Wide Tangent Photon Field Versus Electron Field in the Treatment of Internal Mammary Lymph Nodes in Patients With Left Breast Cancer: A Decision-Making Flowchart.

Purpose: This study of internal mammary lymph node chain (IMC) irradiation in patients with left breast cancer aimed at comparing the merits of using, on one hand, a dedicated direct IMC electron field versus a wide tangent photon field covering both breast and IMC on the other. The objective was to produce guidelines allowing clinicians to readily determine the preferred method for each patient. Methods and Materials: For 19 patients with cancer of the left breast/chest wall, we produced 2 treatment plans each using a different technique: the electron technique using 2 standard opposed photon tangents covering only the breast or chest wall along with a matching adjacent electron field targeting the IMC only or the wide tangent technique using 2 opposed wide tangents covering simultaneously IMC and breast or chest wall. All plans were then optimized for acceptable target coverage. Results: For patients where the left anterior descending coronary artery (LAD) was located outside of the wide tangent fields (13 patients), the wide tangent technique resulted in lower dose to the LAD, left lung, and heart. When the LAD was inside the wide tangents (6 patients), dose was lower with the electron technique for LAD and heart. In all cases, regardless of LAD location, the wide tangent technique returned strictly superior dose homogeneity but much higher right (contralateral) breast dose. Conclusions: A flowchart was produced based on LAD location that allows the clinician to readily determine the preferred technique for each patient without having to perform and compare 2 treatment plans, thus saving valuable planning time.

On the risk of secondary cancer from thymoma radiotherapy.

Objective.This study aims at quantifying the lifetime attributable risk of secondary fatal cancer (LARFAC) to patients receiving adjuvant radiotherapy treatment for thymoma, a neoplasm where cure rates and life expectancy are relatively high, patient age at presentation relatively low and indications for radiotherapy controversial depending on the disease stage.Approach.An anthropomorphic phantom was scanned, organs were contoured and a standard 6 MV 3DCRT treatment plan was produced for thymoma treatment. The phantom was loaded with thermoluminescent dosimeters (TLDs) and treated by linear accelerator per plan. The TLDs were subsequently read for out-of-field dose distribution while in-field dose distribution was obtained from the planning system. Sex and age-specific lifetime radiogenic cancer risk was calculated as the sum of in-field risk and out-of-field risk. The latter risk was estimated using hybrid ICRP 2007 103-BEIR VII tables of organ-specific risks based on the linear-no threshold (LNT) model and applicable at low doses, while the former using mathematical risk models applicable at high doses.Main results.The LARFAC associated with a prescribed dose of 50 Gy to target volume in 25 fractions was in the approximate range of 1%-3%. The risk was higher for young and female patients. The largest contributing organ to this risk were the lungs by far. Using the LNT model inappropriately to calculate risk at therapeutic doses (in-field) would overestimate the risk up to tenfold.Significance.The LARFAC to patient from thymoma radiotherapy was quantified taking into consideration the inapplicability of the LNT model at therapeutic doses. The risk is not negligible; the information may be relevant to patients and clinicians.

Stereotactic Radiosurgery for Atrioventricular Node Ablation in Swine: A Study on Efficacy and Dosimetric Evaluation of Organs at Risk.

Introduction Stereotactic radiosurgery (SRS) delivered to arrhythmogenic foci within the heart is a promising treatment modality. We dosimetrically evaluated the radiation dose to the organs at risk of four swine that were successfully treated with linear-accelerator-based SRS for atrioventricular (AV) node ablation. Materials and methods Single-chamber pacemakers were implanted in four large white breed swine. Cardiac computed tomography simulation scans were performed to localize the AV node and organs at risk. SRS (35-40 Gy) was delivered to the AV node, and the pigs were followed up with pacemaker interrogations. One-sample t-tests were used to evaluate Dmax of great vessels, esophagus, and chest wall as compared to known normal tissue constraints as per RTOG 0631 and AAPM Task Group 101. Results All pigs had disturbances of AV conduction with progressive transition into complete heart block. Macroscopic and microscopic evaluation showed fibrosis in the AV node but did not reveal any changes in non-nodal cardiac tissue or vessels. The mean Dmax±SD (p-value) of the chest wall (14.7±3.3 (0.02)), esophagus (10.7±1.1 (<0.01)) superior vena cava (3.3±4.1 (<0.01)), right pulmonary artery (16.1±6.4 (<0.01)), right pulmonary vein (15.7± 5 (<0.01)), left pulmonary artery (11.1±1.7 (<0.01)) and left pulmonary vein (14.1±2.6 (<0.01)), and the inferior vena cava (33.68±1.6 (0.026)) were significantly below the normal tissue constraint cutoffs. Mean±SD (p-value) of the ascending aorta (19.4±16.1 (0.12)) was not significantly different than normal tissue constraint cutoffs. One swine model treated at 40 Gy had small area of hotspot in the ascending aorta (40.65 (0.4 cc)). Conclusion We have demonstrated in our swine models that SRS using 35-40 Gy can be done without exceeding known human normal tissue constraints to the chest wall, esophagus, and great vessels.

Proton Radiotherapy Could Reduce the Risk of Fatal Second Cancers for Children with Intracranial Tumors in Low- and Middle-Income Countries.

PURPOSE: To test our hypothesis that, for young children with intracranial tumors, proton radiotherapy in a high-income country does not reduce the risk of a fatal subsequent malignant neoplasm (SMN) compared with photon radiotherapy in low- and middle-income countries. MATERIALS AND METHODS: We retrospectively selected 9 pediatric patients with low-grade brain tumors who were treated with 3-dimensional conformal radiation therapy in low- and middle-income countries. Images and contours were deidentified and transferred to a high-income country proton therapy center. Clinically commissioned treatment planning systems of each academic hospital were used to calculate absorbed dose from the therapeutic fields. After fusing supplemental computational phantoms to the patients' anatomies, models from the literature were applied to calculate stray radiation doses. Equivalent doses were determined in organs and tissues at risk of SMNs, and the lifetime attributable risk of SMN mortality (LAR) was predicted using a dose-effect model. Our hypothesis test was based on the average of the ratios of LARs from proton therapy to that of photon therapy ()(H0: = 1; H A : < 1). RESULTS: Proton therapy reduced the equivalent dose in organs at risk for SMNs and LARs compared with photon therapy for which the for the cohort was 0.69 ± 0.10, resulting in the rejection of H0 (P < .001, α = 0.05). We observed that the younger children in the cohort (2-4 years old) were at a factor of approximately 2.5 higher LAR compared with the older children (8-12 years old). CONCLUSION: Our findings suggest that proton radiotherapy has the strong potential of reducing the risk of fatal SMNs in pediatric patients with intracranial tumors if it were made available globally.

On the Feasibility of Stereotactic Radiosurgery With 5.0 and 10.0 mm MLC Leaves as a Function of Target Size and Shape.

Introduction: This study explores the feasibility of SRS/SRT treatment with MLC leaves wider than 2.5 mm at isocenter by inter-comparing treatment plans produced with 2.5, 5.0, and 10.0 mm leaves for various target sizes and shapes. Materials and methods: Forty previously treated patients were re-planned using 2.5, 5.0, and 10.0 mm wide MLC leaves. For each patient, all three plans were evaluated and contrasted between them in terms of five metrics: target dose homogeneity, conformity index, organs at risk dose, dose fall off outside the target, and dose to normal tissues. A regularity index RI was introduced that quantified the degree of target shape irregularity. The effect of target size and shape irregularity on feasibility of 5.0 and 10.0 mm leaves was analyzed. Results: Consistent plan degradation was observed for 10.0 mm (sometimes for 5.0 mm) compared to 2.5 mm MLC in terms of the above five plan metrics, but this degradation was small to clinically insignificant. As an exception, when target (PTV) size was smaller than about 1 cm diameter, clinically significant differences were found between 2.5, 5.0, and 10.0 mm MLC. Conclusion: 5.0 and 10.0 mm MLC can be used in SRS/SRT for targets (PTV) diameter larger than 1 cm. For smaller targets, 2.5 mm MLC is clinically superior, 5.0 is acceptable and 10.0 mm MLC is discouraged in terms of PTV dose conformity.

Predictors of Cardiac Sparing in Deep Inspiration Breath-Hold for Patients With Left Sided Breast Cancer.

Purpose: The purpose of this study was to evaluate patient-related non-dosimetric predictors of cardiac sparing with the use of deep inspiration breath-hold (DIBH) in patients with left-sided breast cancer undergoing irradiation (RT). Materials and Methods: We retrospectively reviewed charts and treatment plans of one-hundred and three patients with left-sided breast cancer. All patients had both free-breathing (FB) and DIBH (with body surface tracking) plans available. (MHD) and V4 (heart volume receiving at least 4 Gy) were extracted from dose volume histograms. Fisher's exact and Chi-square tests were used to identify predictors of reductions in MHD and V4 after DIBH. Results: One-hundred and three patients were identified and most underwent mastectomy. MHD and V4 decreased significantly in DIBH plans (0.74 ± 0.25 Gy vs. 1.72 ± 0.98 Gy, p < 0.0001 for MHD; 4 ± 4.98 cc vs. 20.79 ± 18.2 cc, p < 0.0001 for V4). Body mass index (BMI), smoking and timing of CT simulation (spring/winter vs. summer/fall) were significant predictors of reduction in MHD whereas BMI, field size, chemotherapy, axillary dissection, and timing of CT simulation predicted reduction in V4. On multivariate analysis, BMI, and timing of CT simulation remained significant predictors of the heart-sparing effect of DIBH. Conclusions: In the setting of limited resources, identifying patients who will benefit the most from DIBH is extremely important. Prior studies have identified multiple dosimetric predictors of cardiac sparing and hereby we identified new non-dosimetric factors such as BMI and timing of treatments.

Low- and middle-income countries can reduce risks of subsequent neoplasms by referring pediatric craniospinal cases to centralized proton treatment centers.

Few children with cancer in low- and middle-income countries (LMICs) have access to proton therapy. Evidence exists to support replacing photon therapy with proton therapy to reduce the incidence of secondary malignant neoplasms (SMNs) in childhood cancer survivors. The purpose of this study was to estimate the potential reduction in SMN incidence and in SMN mortality for pediatric medulloblastoma patients in LMICs if proton therapy were made available to them. For nine children of ages 2 to 14 years, we calculated the equivalent dose in organs or tissues at risk for radiogenic SMNs from therapeutic and stray radiation for photon craniospinal irradiation (CSI) in a LMIC and proton CSI in a high-income country. We projected the lifetime risks of SMN incidence and SMN mortality for every SMN site with a widely-used model from the literature. We found that the average total lifetime attributable risks of incidence and mortality were very high for both photon CSI (168% and 41%, respectively) and proton CSI (88% and 26%, respectively). SMNs having the highest risk of mortality were lung cancer (16%), non-site-specific solid tumors (16%), colon cancer (5.9%), leukemia (5.4%), and for girls breast cancer (5.0%) after photon CSI and non-site-specific solid tumors (12%), lung cancer (11%), and leukemia (4.8%) after proton CSI. The risks were higher for younger children than for older children and higher for girls than for boys. The ratios of proton CSI to photon CSI of total risks of SMN incidence and mortality were 0.56 (95% CI, 0.37 to 0.75) and 0.64 (95% CI, 0.45 to 0.82), respectively, averaged over this sample group. In conclusion, proton therapy has the potential to lessen markedly subsequent SMNs and SMN fatalities in survivors of childhood medulloblastoma in LMICs, for example, through regional centralized care. Additional methods should be explored urgently to reduce therapeutic-field doses in organs and tissues at risk for SMN, especially in the lungs, colon, and breast tissues.

Correction factors for diode and diamond detectors in the measurement of small field output factors, using film dosimetry as reference.

The accurate measurement of field output factors at small field sizes typically encountered in SRS and IMRT is challenging. In this study we measured detector output ratios for small fields using a range of detectors and orientations, we then calculated correction factors for each detector using film dosimetry as reference to obtain field output factors. The calculated correction factors were compared to the ones from TRS 483. Detectors used were: EBT3 Gafchromic film, PTW semiflex 31010 chamber, PTW pinpoint 31016 chamber, PTW diamond (used in two different orientations) and PTW SRS 60018 diode. Photon beam energies were 6 MV flat and 7 MV FFF with square field sizes from 0.5 to 10.0 cm side. Semiflex and pinpoint chambers agreed well with film down to 2.0 cm field size but under-responded by up to 40% at 0.5 cm field size. At 0.5 cm field size, diamond with stem parallel to beam axis under-estimated field output factors by up to 6.2%; diamond with stem perpendicular to beam axis over-estimated field output factors by up to 1.5% and diode over-estimated field output factors by up to 6.5%. Calculated correction factors, in general, agreed with and confirmed those given in TRS 483 film is an acceptable alternative to Monte Carlo simulation for deriving correction factors for solid state detectors. For field sizes smaller than 1.0 cm, diamond detector with stem perpendicular to beam axis was the most adequate for field output factor measurement, although not recommended in TRS 483.

Supplemental computational phantoms to estimate out-of-field absorbed dose in photon radiotherapy.

The purpose of this study was to develop a straightforward method of supplementing patient anatomy and estimating out-of-field absorbed dose for a cohort of pediatric radiotherapy patients with limited recorded anatomy. A cohort of nine children, aged 2-14 years, who received 3D conformal radiotherapy for low-grade localized brain tumors (LBTs), were randomly selected for this study. The extent of these patients' computed tomography simulation image sets were cranial only. To approximate their missing anatomy, we supplemented the LBT patients' image sets with computed tomography images of patients in a previous study with larger extents of matched sex, height, and mass and for whom contours of organs at risk for radiogenic cancer had already been delineated. Rigid fusion was performed between the LBT patients' data and that of the supplemental computational phantoms using commercial software and in-house codes. In-field dose was calculated with a clinically commissioned treatment planning system, and out-of-field dose was estimated with a previously developed analytical model that was re-fit with parameters based on new measurements for intracranial radiotherapy. Mean doses greater than 1 Gy were found in the red bone marrow, remainder, thyroid, and skin of the patients in this study. Mean organ doses between 150 mGy and 1 Gy were observed in the breast tissue of the girls and lungs of all patients. Distant organs, i.e. prostate, bladder, uterus, and colon, received mean organ doses less than 150 mGy. The mean organ doses of the younger, smaller LBT patients (0-4 years old) were a factor of 2.4 greater than those of the older, larger patients (8-12 years old). Our findings demonstrated the feasibility of a straightforward method of applying supplemental computational phantoms and dose-calculation models to estimate absorbed dose for a set of children of various ages who received radiotherapy and for whom anatomies were largely missing in their original computed tomography simulations.

Swine Atrioventricular Node Ablation Using Stereotactic Radiosurgery: Methods and In Vivo Feasibility Investigation for Catheter-Free Ablation of Cardiac Arrhythmias.

BACKGROUND: Linear accelerator-based stereotactic radiosurgery delivered to cardiac arrhythmogenic foci could be a promising catheter-free ablation modality. We tested the feasibility of in vivo atrioventricular (AV) node ablation in swine using stereotactic radiosurgery. METHODS AND RESULTS: Five Large White breed swine (weight 40-75 kg; 4 females) were studied. Single-chamber St Jude pacemakers were implanted in each pig. The pigs were placed under general anesthesia, and coronary/cardiac computed tomography simulation scans were performed to localize the AV node. Cone beam computed tomography was used for target positioning. Stereotactic radiosurgery doses ranging from 35 to 40 Gy were delivered by a linear accelerator to the AV node, and the pigs were followed up with weekly pacemaker interrogations to observe for potential electrocardiographic changes. Once changes were observed, the pigs were euthanized, and pathology specimens of various tissues, including the AV node and tissues surrounding the AV node, were taken to study the effects of radiation. All 5 pigs had disturbances of AV conduction with progressive transition into complete heart block. Macroscopic inspection did not reveal damage to the myocardium, and pigs had preserved systolic function on echocardiography. Immunostaining revealed fibrosis in the target region of the AV node, whereas no fibrosis was detected in the nontargeted regions. CONCLUSIONS: Catheter-free radioablation using linear accelerator-based stereotactic radiosurgery is feasible in an intact swine model.

Intraoperative Radiation Therapy: A Promising Treatment Modality in Head and Neck Cancer.

Every year, almost 62,000 are diagnosed with a head and neck cancer (HNC) and 13,000 will succumb to their disease. In the primary setting, intraoperative radiation therapy (IORT) can be used as a boost in select patients in order to optimize local control. Addition of external beam radiation to limited volumes results in improved disease control over surgery and IORT alone. In the recurrent setting, IORT can improve outcomes from salvage surgery especially in patients previously treated with external beam radiation. The use of IORT remains limited to select institutions with various modalities being currently employed including orthovoltage, electrons, and high-dose rate brachytherapy. Practically, execution of IORT requires a coordinated effort and careful planning by a multidisciplinary team involving the head and neck surgeon, radiation oncologist, and physicist. The current review summarizes common uses, outcomes, toxicities, and technical aspects of IORT in HNC patients.

A simple technique for an accurate shielding of the lungs during total body irradiation.

PURPOSE: During total body irradiation (TBI), customized shielding blocks are positioned in front of the lungs to reduce radiation dose. The difficulty is to accurately position the blocks to cover the entire lungs. A new technique based on Computed Tomography (CT) simulation was developed to determine the exact position of lung blocks prior to treatment in order to decrease overall treatment time and reduce patient discomfort. MATERIAL/METHODS: Patients were CT simulated and lungs were contoured using a treatment planning system. Anteroposterior/posteroanterior (AP/PA) fields were designed with MLC aperture conforming to lung contours. The fields were used to represent the extent of the lungs, which was subsequently marked on the patient's skin. The lung blocks were positioned with their shadow matching the lungs' marks. Their position was radiographically verified prior to the delivery of each beam. To evaluate the efficiency of this technique, the treatment session time and the number of repeated attempts to correctly position the shielding blocks was recorded for each beam. Exact treatment times for patients treated with the old technique were not available and were hence approximated based on previous experience. RESULTS: We succeeded in positioning the shielding blocks from the first attempt in 10/12 beams. The position of the shielding blocks was adjusted only one time prior to treatment in 2/12 beams. These results are compared to an average of 3 attempts per beam for each patient using the conventional technique of trial and error. The average time of a treatment session was 29 min with a maximum of 41 min versus approximately 60 min in past treatments and a maximum of 120 min. CONCLUSION: This new technique succeeded in reducing the length of the overall treatment session of the conventional TBI procedure and hence reduced patient discomfort while ensuring accurate shielding of the lungs.

Inter-Institutional Comparison of Personalized Risk Assessments for Second Malignant Neoplasms for a 13-Year-Old Girl Receiving Proton versus Photon Craniospinal Irradiation.

Children receiving radiotherapy face the probability of a subsequent malignant neoplasm (SMN). In some cases, the predicted SMN risk can be reduced by proton therapy. The purpose of this study was to apply the most comprehensive dose assessment methods to estimate the reduction in SMN risk after proton therapy vs. photon therapy for a 13-year-old girl requiring craniospinal irradiation (CSI). We reconstructed the equivalent dose throughout the patient's body from therapeutic and stray radiation and applied SMN incidence and mortality risk models for each modality. Excluding skin cancer, the risk of incidence after proton CSI was a third of that of photon CSI. The predicted absolute SMN risks were high. For photon CSI, the SMN incidence rates greater than 10% were for thyroid, non-melanoma skin, lung, colon, stomach, and other solid cancers, and for proton CSI they were non-melanoma skin, lung, and other solid cancers. In each setting, lung cancer accounted for half the risk of mortality. In conclusion, the predicted SMN risk for a 13-year-old girl undergoing proton CSI was reduced vs. photon CSI. This study demonstrates the feasibility of inter-institutional whole-body dose and risk assessments and also serves as a model for including risk estimation in personalized cancer care.

Analytical model for out-of-field dose in photon craniospinal irradiation.

The prediction of late effects after radiotherapy in organs outside a treatment field requires accurate estimations of out-of-field dose. However, out-of-field dose is not calculated accurately by commercial treatment planning systems (TPSs). The purpose of this study was to develop and test an analytical model for out-of-field dose during craniospinal irradiation (CSI) from photon beams produced by a linear accelerator. In two separate evaluations of the model, we measured absorbed dose for a 6 MV CSI using thermoluminescent dosimeters placed throughout an anthropomorphic phantom and fit the measured data to an analytical model of absorbed dose versus distance outside of the composite field edge. These measurements were performed in two separate clinics-the University of Texas MD Anderson Cancer Center (MD Anderson) and the American University of Beirut Medical Center (AUBMC)-using the same phantom but different linear accelerators and TPSs commissioned for patient treatments. The measurement at AUBMC also included in-field locations. Measured dose values were compared to those predicted by TPSs and parameters were fit to the model in each setting. In each clinic, 95% of the measured data were contained within a factor of 0.2 and one root mean square deviation of the model-based values. The root mean square deviations of the mathematical model were 0.91 cGy Gy(-1) and 1.67 cGy Gy(-1) in the MD Anderson and AUBMC clinics, respectively. The TPS predictions agreed poorly with measurements in regions of sharp dose gradient, e.g., near the field edge. At distances greater than 1 cm from the field edge, the TPS underestimated the dose by an average of 14% ± 24% and 44% ± 19% in the MD Anderson and AUBMC clinics, respectively. The in-field measured dose values of the measurement at AUBMC matched the dose values calculated by the TPS to within 2%. Dose algorithms in TPSs systematically underestimated the actual out-of-field dose. Therefore, it is important to use an improved model based on measurements when estimating out-of-field dose. The model proposed in this study performed well for this purpose in two clinics and may be applicable in other clinics with similar treatment field configurations.

Spectral reconstruction by scatter analysis for a linear accelerator photon beam.

Pre-existing methods for photon beam spectral reconstruction are briefly reviewed. An alternative reconstruction method by scatter analysis for linear accelerators is introduced. The method consists in irradiating a small plastic phantom at standard 100 cm SSD and inferring primary beam energy spectral information based on the measurement with a standard Farmer chamber of scatter around the phantom at several specific scatter angles: a scatter curve is measured which is indicative of the primary spectrum at hand. A Monte Carlo code is used to simulate the scatter measurement set-up and predict the relative magnitude of scatter measurements for mono-energetic primary beams. Based on mono-energetic primary scatter data, measured scatter curves are analysed and the spectrum unfolded as the sum of mono-energetic individual energy bins using the Schiff bremsstrahlung model. The method is applied to an Elekta/SL18 6 MV photon beam. The reconstructed spectrum matches the Monte Carlo calculated spectrum for the same beam within 6.2% (average error when spectra are compared bin by bin). Depth dose values calculated for the reconstructed spectrum agree with physically measured depth dose data to within 1%. Scatter analysis is preliminarily shown to have potential as a practical spectral reconstruction method requiring few measurements under standard 100 cm SSD and feasible in any radiotherapy department using a phantom and a Farmer chamber.