Individualised selection of left-sided breast cancer patients for proton therapy based on cost-effectiveness.

INTRODUCTION: The significantly greater cost of proton therapy compared with X-ray therapy is frequently justified by the expected reduction in normal tissue toxicity. This is often true for indications such as paediatric and skull base cancers. However, the benefit is less clear for other more common indications such as breast cancer, and it is possible that the degree of benefit may vary widely between these patients. The aim of this work was to demonstrate a method of individualised selection of left-sided breast cancer patients for proton therapy based on cost-effectiveness of treatment. METHODS: 16 left-sided breast cancer patients had a treatment plan generated for the delivery of intensity-modulated proton therapy (IMPT) and of intensity-modulated photon therapy (IMRT) with the deep inspiration breath-hold (DIBH) technique. The resulting dosimetric data was used to predict probabilities of tumour control and toxicities for each patient. These probabilities were used in a Markov model to predict costs and the number of quality-adjusted life years expected as a result of each of the two treatments. RESULTS: IMPT was not cost-effective for the majority of patients but was cost-effective where there was a greater risk reduction of second malignancies with IMPT. CONCLUSION: The Markov model predicted that IMPT with DIBH was only cost-effective for selected left-sided breast cancer patients where IMRT resulted in a significantly greater dose to normal tissue. The presented model may serve as a means of evaluating the cost-effectiveness of IMPT on an individual patient basis.

Validation of a new open-source method for automatic delineation and dose assessment of the heart and LADCA in breast radiotherapy with simultaneous uncertainty estimation.

Radiotherapy has been shown to increase risks of cardiotoxicities for breast cancer patients. Automated delineation approaches are necessary for consistent and efficient assessment of cardiac doses in large, retrospective datasets, while patient-specific estimation of the uncertainty in these doses provides valuable additional data for modelling and understanding risks. In this work, we aim to validate the consistency of our previously described open-source software model for automatic cardiac delineation in the context of dose assessment, relative to manual contouring. We also extend our software to introduce a novel method to automatically quantify the uncertainty in cardiac doses based on expected inter-observer variability (IOV) in contouring. This method was applied to a cohort of 15 left-sided breast cancer patients treated in Denmark using modern tangential radiotherapy techniques. On each image set, the whole heart and left anterior descending coronary artery (LADCA) were contoured by nine independent experts; the range of doses to these nine volumes provided a reference for the dose uncertainties generated from the automatic method. Local and external atlas sets were used to test the method. Results give confidence in the consistency of automatic segmentations, with mean whole heart dose differences for local and external atlas sets of -0.20 ± 0.17 and -0.10 ± 0.14 Gy, respectively. Automatic estimates of uncertainties in doses are similar to those from IOV for both the whole heart and LADCA. Overall, this study confirms that our automated approach can be used to accurately assess cardiac doses, and the proposed method can provide a useful tool in estimating dose uncertainties.

Variations in Medicaid Payment Rates for Radiation Oncology.

PURPOSE: Interstate variations in Medicaid reimbursements can be significant, and patients who live in states with low Medicaid reimbursements tend to have worse access to care. This analysis describes the extent of variations in Medicaid reimbursements for radiation oncology services across the United States. METHODS AND MATERIALS: The Current Procedural Terminology codes billed for a course of whole breast radiation were identified for this study. Publicly available fee schedules were queried for all 50 states and Washington, DC, to determine the reimbursement for each service and the total reimbursement for the entire episode of care. The degree of interstate payment variation was quantified by computing the range, mean, standard deviation, and coefficient of variation. The cost of care for the entire episode of treatment was compared to the publicly available Kaiser Family Foundation (KFF) Medicaid-to-Medicare fee index to determine if the pattern of payment variation in medical services generally is predictive of the variation seen in radiation oncology specifically. RESULTS: Data were available for 48 states and Washington, DC. The total episode reimbursement (excluding image guidance for respiratory tracking) varied from $2945 to $15,218 (mean, $7233; standard deviation, $2248 or 31%). The correlation coefficient of the KFF index to the calculated entire episode of care for each state was 0.55. CONCLUSIONS: There is considerable variability in coverage and payments rates for radiation oncology services under Medicaid, and these variations track modestly with broader medical fees based on the KFF index. These variations may have implications for access to radiation oncology services that warrant further study.

External beam accelerated partial breast irradiation: dosimetric assessment of conformal and three different intensity modulated techniques.

Background The aim of the study was to evaluate and compare four different external beam radiotherapy techniques of accelerated partial breast irradiation (APBI) considering target coverage, dose to organs at risk and overall plan quality. The investigated techniques were three dimensional conformal radiotherapy (3D-CRT), "step and shoot" (SS) and "sliding window" (SW) intensity-modulated radiotherapy (IMRT), intensity-modulated arc therapy (RA). Patients and methods CT scans of 40 APBI patients were selected for the study. The planning objectives were set up according to the international recommendations. Homogeneity, conformity and plan quality indices were calculated from volumetric and dosimetric parameters of target volumes and organs at risk. The total monitor units and feasibility were also investigated. Results There were no significant differences in the coverage of the target volume between the techniques. The homogeneity indices of 3D-CRT, SS, SW and RA plans were 0.068, 0.074, 0.058 and 0.081, respectively. The conformation numbers were 0.60, 0.80, 0.82 and 0.89, respectively. The V50% values of the ipsilateral breast for 3D-CRT, SS, SW and RA were 47.5%, 40.2%, 39.9% and 31.6%, respectively. The average V10% and V40% values of ipsilateral lung were 13.1%, 28.1%, 28%, 36% and 2.6%, 1.9%, 1.9%, 3%, respectively. The 3D-CRT technique provided the best heart protection, especially in the low dose region. All contralateral organs received low doses. The SW technique achieved the best plan quality index (PQI). Conclusions Good target volume coverage and tolerable dose to the organs at risk are achievable with all four techniques. Taking into account all aspects, we recommend the SW IMRT technique for APBI.

Assessment of a guideline-based heart substructures delineation in left-sided breast cancer patients undergoing adjuvant radiotherapy : Quality assessment within a randomized phase III trial testing a cardioprotective treatment strategy (SAFE-2014).

BACKGROUND AND PURPOSE: In our institute, breast cancer patients undergoing adjuvant treatment are included in a protocol aimed to reduce cardiovascular morbidity (SAFE-2014, NCT2236806), assessing preclinical heart damage with heart speckle-tracking ultrasound. To develop a dose constraint related to subclinical heart damage, a reliable delineation of heart substructures based on a pre-existing guideline was made. PATIENTS AND METHODS: Heart substructures of 16 left-sided breast cancer patients included in the SAFE protocol were delineated by five operators. For each substructure, a multi-contour delineation based on a majority vote algorithm (MCD) was created. A consensus-based delineation (CBD) was developed by an independent team of two blinded operators. Dice similarity coefficients (DSC) between volumes delineated by different operators and the MCD were collected and reported, as well as DSC between CBD and MCD. RESULTS: Mean DSCs between heart chambers delineated by each operator and the corresponding MCDs ranged between 0.78 and 0.96. Mean DSC between substructures delineated by all single operators and the corresponding MCD ranged between 0.84 and 0.94. Mean DSC between CBD and the corresponding MCD ranged from 0.89 to 0.97. CONCLUSION: Results showed low inter-observer variability of heart substructure delineation. This constitutes an external validation of the contouring atlas used, allowing a reliable dosimetric assessment of these volumes within the SAFE-2014 trial.

Heart toxicity from breast cancer radiotherapy : Current findings, assessment, and prevention.

BACKGROUND: Late cardiac toxicities caused by (particularly left-sided) breast radiotherapy (RT) are now recognized as rare but relevant sequelae, which has prompted research on risk structure identification and definition of threshold doses to heart subvolumes. The aim of the present review was to critically discuss the clinical evidence on late cardiac reactions based on dose-dependent outcome reports for mean heart doses as well as doses to cardiac substructures. METHODS: A literature review was performed to examine clinical evidence on radiation-induced heart toxicities. Mean heart doses and doses to cardiac substructures were focused upon based on dose-dependent outcome reports. Furthermore, an overview of radiation techniques for heart protection is given and non-radiotherapeutic aspects of cardiotoxicity in the multimodal setting of breast cancer treatment are discussed. RESULTS: Based on available findings, the DEGRO breast cancer expert panel recommends the following constraints: mean heart dose <2.5 Gy; DmeanLV (mean dose left ventricle) < 3 Gy; V5LV (volume of LV receiving ≥5 Gy) < 17%; V23LV (volume of LV receiving ≥23 Gy) < 5%; DmeanLAD (mean dose left descending artery) < 10 Gy; V30LAD (volume of LAD receiving ≥30 Gy) < 2%; V40LAD (volume of LAD receiving ≥40 Gy) < 1%. CONCLUSION: In addition to mean heart dose, breast cancer RT treatment planning should also include constraints for cardiac subvolumes such as LV and LAD. The given constraints serve as a clinicians' aid for ensuring adequate heart protection. The individual decision between sufficient protection of cardiac structures versus optimal target volume coverage remains in the physician's hand. The risk of breast cancer-specific mortality and a patient's cardiac risk factors must be individually weighed up against the risk of radiation-induced cardiotoxicity.

Assessment of deep inspiration breath hold (DIBH) amplitude and reduction in cardiac dose in left breast cancer patients.

INTRODUCTION: The primary aim of this study was to examine the impact of deep inspiration breath-hold (DIBH) amplitude on subsequent mean heart dose and V30 during radiotherapy. The secondary aim was to investigate if patient age influenced DIBH amplitude. METHOD: A retrospective study of 30 patients with left-sided breast cancer was completed. Patients were randomly selected from the total number of patients dual scanned in free breathing (FB) and DIBH over a 2-year period. Plans were retrospectively virtually simulated and statistical analysis performed. RESULTS: All patients achieved decreased V30 and mean cardiac dose using DIBH. A positive correlation was found between DIBH amplitude and cardiac V30 dose reduction (p = 0.007, R = 0.48). Ratio of amplitude increase from FB to DIBH and cardiac V30 reduction was positively correlated and statistically significant (p = 0.04, R = 0.38); Ratio of amplitude increase of at least 15 times FB achieved 100% V30 dose reduction, however this was also achieved with ratio increase as low as 6.25 times FB. A statistically significant positive correlation was identified between DIBH amplitude and mean cardiac dose reduction (p = 0.003, R = 0.523). No correlation was found between patient age and amplitude ratio increase (p = 0.602, R = -0.099). CONCLUSION: A 100% reduction in cardiac V30 can be achieved with a DIBH amplitude increase of 15 times FB. A full reduction can also be achieved at much lower levels (6.25 times FB in current study); however there appears to be no pre-determining patient factors to identify this. DIBH amplitudes of 1 cm-4 cm reduce cardiac mean dose by at least 50%.

Resource requirements and reduction in cardiac mortality from deep inspiration breath hold (DIBH) radiation therapy for left sided breast cancer patients: A prospective service development analysis.

INTRODUCTION: Use of deep inspiration breath hold (DIBH) radiation therapy may reduce long-term cardiac mortality. The resource and time commitments associated with DIBH are impediments to its widespread adoption. We report the dosimetric benefits, workforce requirements, and potential reduction in cardiac mortality when DIBH is used for left-sided breast cancers. METHODS AND MATERIALS: Data regarding the time consumed for planning and treating 50 patients with left-sided breast cancer with DIBH and 20 patients treated with free breathing (FB) radiation therapy were compiled prospectively for all personnel (regarding person-hours [PH]). A second plan was generated for all DIBH patients in the FB planning scan, which was then compared with the DIBH plan. Mortality reduction from use of DIBH was calculated using the years of life lost resulting from ischemic heart disease for Indians and the postulated reduction in risk of major cardiac events resulting from reduced cardiac dose. RESULTS: The median reduction in mean heart dose between the DIBH and FB plans was 166.7 cGy (interquartile range, 62.7-257.4). An extra 6.76 PH were required when implementing DIBH as compared with FB treatments. Approximately 3.57 PH were necessary per Gy of reduction in mean heart dose. The excess years of life lost from ischemic heart disease if DIBH was not done in was 0.95 per 100 patients, which translates into a saving of 12.8 hours of life saved per PH of work required for implementing DIBH. DIBH was cost effective with cost for implementation of DIBH for all left-sided breast cancers at 2.3 times the annual per capita gross domestic product. CONCLUSION: Although routine implementation of DIBH requires significant resource commitments, it seems to be worthwhile regarding the projected reductions in cardiac mortality.

Assessment of radiation-induced secondary cancer risk in the Brazilian population from left-sided breast-3D-CRT using MCNPX.

OBJECTIVE: The aim of this work was to simulate a 6MV conventional breast 3D conformational radiation therapy (3D-CRT) with physical wedges (50 Gy/25#) in the left breast, calculate the mean absorbed dose in the body organs using robust models and computational tools and estimate the secondary cancer-incidence risk to the Brazilian population. METHODS: The VW female phantom was used in the simulations. Planning target volume (PTV) was defined in the left breast. The 6MV parallel-opposed fields breast-radiotherapy (RT) protocol was simulated with MCNPx code. The absorbed doses were evaluated in all the organs. The secondary cancer-incidence risk induced by radiotherapy was calculated for different age groups according to the BEIR VII methodology. RESULTS: RT quality indexes indicated that the protocol was properly simulated. Significant absorbed dose values in red bone marrow, RBM (0.8 Gy) and stomach (0.6 Gy) were observed. The contralateral breast presented the highest risk of incidence of a secondary cancer followed by leukaemia, lung and stomach. The risk of a secondary cancer-incidence by breast-RT, for the Brazilian population, ranged between 2.2-1.7% and 0.6-0.4%. CONCLUSION: RBM and stomach, usually not considered as OAR, presented high second cancer incidence risks of 0.5-0.3% and 0.4-0.1%, respectively. This study may be helpful for breast-RT risk/benefit assessment. Advances in knowledge: MCNPX-dosimetry was able to provide the scatter radiation and dose for all body organs in conventional breast-RT. It was found a relevant risk up to 2.2% of induced-cancer from breast-RT, considering the whole thorax organs and Brazilian cancer-incidence.

Assessment of voluntary deep inspiration breath-hold with CINE imaging for breast radiotherapy.

Deep Inspiration Breath-Hold (DIBH) techniques for breast cancer radiation therapy (RT) have reduced cardiac dose compared to Free Breathing (FB). Recently, a voluntary deep inspiration breath-hold (vDIBH) technique was established using in-room lasers and skin tattoos to monitor breath-hold. An in-house quality assessment of positional reproducibility during RT delivery with vDIBH in patients with left-sided breast cancer was evaluated. The electronic portal imaging device (EPID) was used in cinematographic (CINE) mode to capture a sequence of images during beam delivery. Weekly CINE images were retrospectively assessed for 20 left-sided breast cancer patients receiving RT in vDIBH, and compared with CINE images of 20 patients treated in FB. The intra-beam motion was assessed and the distance from the beam central axis (CA) to the internal chest wall (ICW) was measured on each CINE image. These were then compared to the planned distance on digitally reconstructed radiograph (DRR). The maximum intra-beam motion for any one patient measurement was 0.30 cm for vDIBH and 0.20 cm for FB. The mean difference between the distance from the CA to ICW on DRR and the equivalent distance on CINE imaging (as treated) was 0.28 cm (SD 0.17) for vDIBH patients and 0.25 cm (SD 0.14) for FB patients (P = 0.458). The measured values were comparable for patients undergoing RT in vDIBH, and for those in FB. This quality assessment showed that using in-room lasers and skin tattoos to independently monitor breath-hold in vDIBH as detected by 'on-treatment' CINE imaging is safe and effective.

Assessment of Intrafraction Breathing Motion on Left Anterior Descending Artery Dose During Left-Sided Breast Radiation Therapy.

PURPOSE: To use 4-dimensional computed tomography (4D-CT) imaging to predict the level of uncertainty in cardiac dose estimates of the left anterior descending artery that arises due to breathing motion during radiation therapy for left-sided breast cancer. METHODS AND MATERIALS: The fast helical CT (FH-CT) and 4D-CT of 30 left-sided breast cancer patients were retrospectively analyzed. Treatment plans were created on the FH-CT. The original treatment plan was then superimposed onto all 10 phases of the 4D-CT to quantify the dosimetric impact of respiratory motion through 4D dose accumulation (4D-dose). Dose-volume histograms for the heart, left ventricle (LV), and left anterior descending (LAD) artery obtained from the FH-CT were compared with those obtained from the 4D-dose. RESULTS: The 95% confidence interval of 4D-dose and FH-CT differences in mean dose estimates for the heart, LV, and LAD were ±0.5 Gy, ±1.0 Gy, and ±8.7 Gy, respectively. CONCLUSION: Fast helical CT is a good approximation for doses to the heart and LV; however, dose estimates for the LAD are susceptible to uncertainties that arise due to intrafraction breathing motion that cannot be ascertained without the additional information obtained from 4D-CT and dose accumulation. For future clinical studies, we suggest the use of 4D-CT-derived dose-volume histograms for estimating the dose to the LAD.

Modern Radiation Therapy and Cardiac Outcomes in Breast Cancer.

PURPOSE: Adjuvant radiation therapy, which has proven benefit against breast cancer, has historically been associated with an increased incidence of ischemic heart disease. Modern techniques have reduced this risk, but a detailed evaluation has not recently been conducted. The present study evaluated the effect of current radiation practices on ischemia-related cardiac events and procedures in a population-based study of older women with nonmetastatic breast cancer. METHODS AND MATERIALS: A total of 29,102 patients diagnosed from 2000 to 2009 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Medicare claims were used to identify the radiation therapy and cardiac outcomes. Competing risk models were used to assess the effect of radiation on these outcomes. RESULTS: Patients with left-sided breast cancer had a small increase in their risk of percutaneous coronary intervention (PCI) after radiation therapy-the 10-year cumulative incidence for these patients was 5.5% (95% confidence interval [CI] 4.9%-6.2%) and 4.5% (95% CI 4.0%-5.0%) for right-sided patients. This risk was limited to women with previous cardiac disease. For patients who underwent PCI, those with left-sided breast cancer had a significantly increased risk of cardiac mortality with a subdistribution hazard ratio of 2.02 (95% CI 1.23-3.34). No other outcome, including cardiac mortality for the entire cohort, showed a significant relationship with tumor laterality. CONCLUSIONS: For women with a history of cardiac disease, those with left-sided breast cancer who underwent radiation therapy had increased rates of PCI and a survival decrement if treated with PCI. The results of the present study could help cardiologists and radiation oncologists better stratify patients who need more aggressive cardioprotective techniques.

Prospective assessment of deep inspiration breath-hold using 3-dimensional surface tracking for irradiation of left-sided breast cancer.

PURPOSE: Deep inspiration breath hold (DIBH) is used to decrease cardiac irradiation during radiation therapy (RT) for breast cancer. The patients most likely to benefit and the impact on treatment time remain largely unknown. We sought to identify predictors for the use of DIBH and to quantify differences in dosimetry and treatment time using a prospective registry. METHODS AND MATERIALS: A total of 150 patients with left breast cancer were enrolled. All patients were simulated with both free breathing (FB) and DIBH. RT was delivered by either modality. Alternate scans were planned with use of deformable registration to include identical RT volumes. DIBH patients were monitored by a real-time surface tracking system, AlignRT (Vision RT, Ltd, London, United Kingdom). Baseline characteristics and treatment times were compared by Fisher exact test and Wilcoxon rank sum test. Dosimetric endpoints were analyzed by Wilcoxon signed rank test, and linear regression identified predictors for change in mean heart dose (∆MHD). RESULTS: We treated 38 patients with FB and 110 with DIBH. FB patients were older, more likely to have heart and lung disease, and less likely to receive chemotherapy or immediate reconstruction (all P < .05). Treatment times were not significantly different, but DIBH patients had greater variability in times (P = .0002). Of 146 evaluable patients, DIBH resulted in >20 cGy improvement in MHD in 107 patients but a >20 cGy increase in MHD in 14. Both MHD and lung V20 were significantly lower in DIBH than in paired FB plans. On multivariate analysis, younger age (4.18 cGy per year; P < .0001), higher body mass index (6.06 cGy/kg/m(2); P = .0018), and greater change in lung volumes (130 cGy/L; P = .003) were associated with greater ∆MHD. CONCLUSIONS: DIBH improves cardiac dosimetry without significantly impacting treatment time in most patients. Greater inspiratory lung volumes augment this benefit. Because the improvement with DIBH was not uniform, patients should be scanned with both FB and DIBH.