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Voxel-based anthropomorphic phantom from a radiotherapy planning CT scan obtained from a 21 year-old female adult. A: Example of field set-up type 11C, B: location and size of the breast cancer in the left breast drawn on the appropriate position in the CT-based phantom with colour-wash of dose distribution. C: determination of the position of subsequent breast cancer (BC) drawn onto the simulation radiograph of the individual patient (for use with the radiograph-based method).
Source publication
Background
An increased risk of breast cancer following radiotherapy for Hodgkin lymphoma (HL) has now been robustly established. In order to estimate the dose–response relationship more accurately, and to aid clinical decision making, a retrospective estimation of the radiation dose delivered to the site of the subsequent breast cancer is required...
Contexts in source publication
Context 1
... radiation dosimetry was based on a voxel-based anthropo- morphic phantom from a radiotherapy planning CT scan obtained from a typical 21 year-old female HL patient, with height 1.70 m and weight 67 kg. (Fig. 1). The scan was acquired in supine position on a flat couch top with the arms abducted alongside the head. We first established a library of the different shapes and combinations of radiation field set-ups based on the treatment charts of patients who had developed breast cancer following HL treatment and also their controls without ...
Context 2
... used was 0.04. As the prescribed dose for the same field type varied per patient, the dose scale was set as a percentage of the prescribed dose to the target volume. The dose distribution was reported in 12 transversal planes at 1.5 cm intervals, from the second to the 10th thoracic vertebrae, covering the whole breast tissue in the phantom (Fig. 1). Finally, a pdf file with hyperlinks was produced for each typical field allow- ing access to the dose distribution on a transversal CT slice by a mouse click and thus provide an interactive and user friendly dosimetry ...
Citations
... Breast tissue was mapped to a grid of approximately 300 000, 2 x 2 x 2 mm 3 voxels. The proportion of prescribed dose to each voxel was estimated for each field setup (22) using the Isogray treatment planning system (Dosisoft, Cachan, France). Individual distributions of absorbed dose were estimated by multiplying the field setup dosimetry with the patient's prescribed dose(s) and summing over all fields the patient received. ...
... In our previous analysis of the same data (10) Our study is the first evaluation of dose and DVH metrics as determinants of BC among HL survivors. Several limitations might have contributed to the failure of DVH metrics to substantially improve the models, including uncertainty in reconstruction of historic 3D dose distributions, although systematic errors are unlikely (22). Some field types were very common, and many were variations of similar (mantle) fields ( Supplementary Figures 1 and 2, available online), that is, most dose-volume metrics were highly correlated. ...
Background
Breast cancer (BC) risk is increased among Hodgkin lymphoma (HL) survivors treated with chest radiotherapy. Case-control studies showed a linear radiation dose-response relationship for estimated dose to the breast tumor location. However, these relative risks cannot be used for absolute risk prediction of BC anywhere in the breasts. Furthermore, the independent and joint effects of radiation dose and irradiated volumes are unclear. Therefore, we examined the effects of mean breast dose and various dose-volume parameters on BC risk in HL patients.
Methods
We conducted a nested case-control study of BC among five-year HL survivors (173 cases, 464 matched controls). Dose-volume histograms (DVHs) were obtained from reconstructed voxel-based three-dimensional dose distributions. Summary parameters of DVH were studied next to mean and median breast dose, Gini index and the new dose metric mean absolute difference (MAD) of dose, using categorical and linear excess odds ratio (EOR) models. Interactions between dose-volume parameters and mean dose were also examined.
Results
Statistically significant linear dose-response relationships were observed for mean breast dose (EOR/Gy: 0.19; 95% confidence interval [CI]: 0.05 to 1.06) and median dose (EOR/Gy: 0.06; 95% CI: 0.02 to 0.19), with no statistically significant curvature. All metrics except Gini and MAD were positively correlated with each other. These metrics all showed similar patterns of dose-response that were no longer statistically significant when adjusting for mean dose. No statistically significant modification of the effect of mean dose was observed.
Conclusion
Mean breast dose predicts subsequent BC risk in long-term HL survivors.
... Nonetheless, a number of authors (e.g. Stovall et al 2006, Kry et al 2017, Russell et al 2017, Newhauser et al 2018, Howell et al 2019, Schonfeld et al 2020 have examined methods of reconstructing tissue doses received during radiation therapy, both inside and outside the radiation field, particularly for the purposes of epidemiological studies of survivors. These dosimetry studies are crucial to a proper understanding of the risk of second primary cancers. ...
It is established that moderate-to-high doses of ionising radiation increase the risk of subsequent cancer in the exposed individual, but the question arises as to the risk of cancer from higher doses, such as those delivered during radiotherapy, accidents, or deliberate acts of malice. In general, the cumulative dose received during a course of radiation treatment is sufficiently high that it would kill a person if delivered as a single dose to the whole body, but therapeutic doses are carefully fractionated and high/very high doses are generally limited to a small tissue volume under controlled conditions. The very high cumulative doses delivered as fractions during radiation treatment are designed to inactivate diseased cells, but inevitably some healthy cells will also receive high/very high doses. How the doses (ranging from <1 Gy to tens of Gy) received by healthy tissues during radiotherapy affect the risk of second primary cancer is an increasingly important issue to address as more cancer patients survive the disease. Studies show that, except for a turndown for thyroid cancer, a linear dose-response for second primary solid cancers seems to exist over a cumulative gamma radiation dose range of tens of gray, but with a gradient of excess relative risk (ERR) per Gy that varies with the type of second cancer, and which is notably shallower than that found in the Japanese atomic bomb survivors receiving a single moderate-to-high acute dose. The risk of second primary cancer consequent to high/very high doses of radiation is likely to be due to repopulation of heavily irradiated tissues by surviving stem cells, some of which will have been malignantly transformed by radiation exposure, although the exact mechanism is not known, and various models have been proposed. It is important to understand the mechanisms that lead to the raised risk of second primary cancers consequent to the receipt of high/very high doses, in particular so that the risks associated with novel radiation treatment regimens – for example, intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) that deliver high doses to the target volume while exposing relatively large volumes of healthy tissue to low/moderate doses, and treatments using protons or heavy ions rather than photons – may be properly assessed.
... According to an evaluation of 4932 patients with metastatic BC between 2010 and 2013, 17% of patients were ≤ 50, 51% of patients were between 50 and 69 years old and 31% of patients were > 69 years old [5,6]. In addition, in a study of 2097 patients, the mean age of diagnosis was 55.9 ± 38.1 years old [7]. ...
The aim of this study is to determine the relationship between the demographics and the clinical characteristics of breast cancer (BC) patients with bone metastasis (BM). The study included 1100 BC patients, of whom 174 had BMs and 926 had no BMs. Immunohistochemical methods were employed to understand estrogen receptor (ER)/progesterone receptor (PgR) receptor levels, Ki-67 protein levels and human epidermal growth factor receptor 2 (HER2) expression levels. Data were collected based on the hospital records of these patients, and ultrasonography or magnetic resonance imaging (MRI) results were employed for tumor localization. Positron emission tomography (PET)-computed tomography (CT) data were employed for the BM evaluation. The mean age (P =0.067) and tumor diameter (P = 0.022) of BC cases who showed BM were significantly different from those who did not show BM. In addition, a significant relationship between the tumor diameter (P = 0.001) and axillary lymph node (ALN) number (P = 0.000) and BM was observed. The percentages of ER and PgR (r = 0.639; P = 0.000) were positively correlated, while the percentage of ER and Ki-67 protein levels (r = -0.505; P = 0.000) were negatively correlated. However, these correlations were not significant between the groups. The tumor diameter and positive ALNs may have an important role in BM of BC. There was no significant effect of ER/PgR receptor levels, Ki 67 protein levels, or HER2 expression levels in BMs of BC.
... Logistic regression analyses showed that increased breast field separation positively correlated with increased radiation dermatitis severity (p = 0.018). Breast field separation can be used to estimate breast size [13,29,33]. We performed a subgroup analysis on patients with a breast field separation of ≥ 25 cm who were more likely to have a severe radiationinduced skin reaction (n = 22). ...
Purpose
Although topical agents are often provided during radiation therapy, there is limited consensus and evidence for their use prophylactically to prevent or reduce radiation dermatitis.
Methods
This was a multi-site, randomized, placebo-controlled, blinded study of 191 breast cancer patients to compare the prophylactic effectiveness of three topical agents (Curcumin, HPR Plus™, and Placebo) for reducing radiation dermatitis and associated pain. Patients applied the topical agent to their skin in the radiation area site three times daily starting the first day of radiation therapy (RT) until 1 week after RT completion.
Results
Of the 191 randomized patients, 171 patients were included in the final analyses (87.5% white females, mean age = 58 (range = 36–88)). Mean radiation dermatitis severity (RDS) scores did not significantly differ between study arms (Curcumin = 2.68 [2.49, 2.86]; HPR Plus™ = 2.64 [2.45, 2.82]; Placebo = 2.63 [2.44, 2.83]; p = 0.929). Logistic regression analyses showed that increased breast field separation positively correlated with increased radiation dermatitis severity (p = 0.018). In patients with high breast field separation (≥ 25 cm), RDS scores (Curcumin = 2.70 [2.21, 3.19]; HPR Plus™ = 3.57 [3.16, 4.00]; Placebo = 2.95 [2.60, 3.30]; p = 0.024) and pain scores (Curcumin = 0.52 [− 0.28, 1.33]; HPR Plus™ = 0.55 [− 0.19, 1.30]; Placebo = 1.73 [0.97, 2.50]; p = 0.046) significantly differed at the end of RT.
Conclusions
Although there were no significant effects of the treatment groups on the overall population, our exploratory subgroup analysis suggests that prophylactic treatment with topical curcumin may be effective for minimizing skin reactions and pain for patients with high breast separation (≥ 25 cm) who may have the worst skin reactions.
... However, there are few studies that distinguish a 10.0 mm or greater deep tumor in tissue from surface because it is too deep for deformation and vibration on the tissue surface to show differences in tumor types. Generally, although most researches discuss about the surface position of the breast cancer [19], the breast cancer depth is important because the breast cancer often come around the Mammary gland [20,21]. Since mammary grand is deeply located in the breast, it's important to distinguish the type of the breast cancer located deeply. ...
... A simulated tumor was colored with the colorant KE-COLOR-BR, with the proportion of colorant set at 1% so as not to affect the physical properties of the material. The tumor diameter was 14.0 mm because the tumor size less than 20.0 mm is early breast cancer [19]. ...
Breast cancer diagnosis has been mostly accomplished through imaging. These methods have great advantages in being able to detect the presence and location of breast cancer. However, it is difficult to distinguish between a benign and malignant tumor located in a deep position because both tumor types look similar. In this paper, tissue including the tumor from skin was vibrated using a compression cylinder, to analyze the frequency difference for distinguishing tissue type. Before distinguishing between a benign and malignant tumor, it is necessary to validate that the difference between normal tissue and tumor can be distinguished. The objective of the study is to validate the feasibility to emphasize the frequency differences in a 10.0 mm or greater deep tumors during vibration by pushing a cylinder towards the deep tumor. A phantom model and finite element analysis model were constructed to simulate the breast. In the experiment, air was injected into the phantom and the displacement was measured. The frequency response for distinction of tissue types was analyzed and it was found that the displacement difference rate was over 50% at a frequency of 130 Hz when the cylinder was pushed into the sample as opposed to when not pushed in. Changes in displacement were measured according to the distance between the tumor and vibration point using finite element analysis. When the measurement and vibration points were on the center of the tumor, the difference in the resonance point was at its largest (5.5 Hz). Results show that the position of a tumor could be easily and rapidly detected by vibrations from a cylinder pushed into the diagnostic site.
Second breast cancer (SBC) is the most common solid cancer among Hodgkin Lymphoma (HL) female survivors. We reviewed the related modifying risk factors, radiation-induced carcinogenesis, tumors characteristics, management specificities, prevention and
surveillance modalities based on current evidence. The risk of developing SBC may be influenced essentially by the age at HL treatment, follow-up latency, dose of irradiation received and the extent of irradiated field. SBCs generally develop at younger age, they are often bilateral, and exhibit more aggressive biological features and worse prognosis. No firm answer about the benefits of breast surveillance is provided by literature, but compelling evidence tends toward a clinical benefit in early detection. Increasing awareness among health providers’ care and current survivors as well as the implementation of screening measures is crucial. Great efforts are ongoing in individualizing treatment strategies for future HL patients and response-adapted approaches are holding promise in prevention of these second malignancies.
