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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Breast cancer is the most common malignancy among women&#44; excluding non-melanoma skin cancers&#46; Radiotherapy plays an important role in locoregional and distant control of this neoplasm&#44; increasing disease-free survival and overall survival rates by up to 20&#37; in 20 years&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> Therefore&#44; radiotherapy is indicated for all patients submitted to conservative surgery and for those undergoing mastectomy&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">One of the main adverse reactions of adjuvant radiotherapy in the breast is radiodermatitis&#46; Approximately 85&#37;&#8210;90&#37; of the patients develop some degree of this reaction&#44; which can manifest itself with variable severity&#46; Radiation promotes several skin changes&#44; including increased pH&#44; decreased hydration&#44; increased cutaneous blood flow&#44; and hyperpigmentation&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#8211;5</span></a> Skin toxicities manifest as erythema&#44; hyperpigmentation&#44; desquamation&#44; exulceration&#44; ulceration&#44; and necrosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The consequences of radiodermatitis are numerous and include decreased quality of life due to pain and discomfort&#44; infection&#44; decreased self-image&#44; and radiotherapy interruption&#44; impairing neoplasm control&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Several factors have been associated with the cutaneous toxicity of radiotherapy&#44; such as the three-dimensional breast shape and the treatment technique&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a> Comorbidities&#44; concomitant chemotherapy&#44; sun exposure&#44; high-dose radiation&#44; tumor location&#44; and staging have been identified as related to radiodermatitis&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#8211;14</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Iwakawa et al&#46; demonstrated that the risk of skin reactions in the breast was highly dependent on the institution where the patient was treated due to different treatment techniques&#44; surgical procedures&#44; magnitudes of photon and electron energy&#44; use of multi-blade collimators&#44; immobilization devices&#44; and wedge filters&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Therefore&#44; it is necessary to better understand the factors associated with the development of radiodermatitis in these patients&#44; considering the different realities of radiotherapy services and the different populations served&#46; In this context&#44; this study aimed to evaluate the incidence of radiodermatitis in women with breast cancer&#44; identify the factors associated with its severity and determine the time in which this adverse reaction occurs during radiotherapy&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Study type&#44; location and participants</span><p id="par0035" class="elsevierStylePara elsevierViewall">This was a prospective and analytical cohort study carried out in the radiotherapy sector of the Clinical Hospital of Botucatu Medical School &#8211; S&#227;o Paulo State University &#8220;J&#250;lio de Mesquita Filho&#46; Inclusion criteria were women over 18 years of age&#44; diagnosed with breast cancer&#44; and an indication of radiotherapy with photon emission by the radiotherapist&#46; This indication was for adjuvant radiotherapy treatment after an interval of 21 days post-chemotherapy&#44; complete healing of the surgical wound&#44; and free movement of the ipsilateral upper limb&#46; Patients with skin changes in the breast prior to radiotherapy were excluded due to interference in the evaluation&#44; as well as patients with limited mobility due to the difficulty in performing the study procedures&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The study was approved by the Research Ethics Committee of the University Hospital &#40;CAAE&#58; 62865916&#46;2&#46;0000&#46;5411&#41; and conducted in accordance with the recommendations of Resolution n&#46; 466&#47;12 &#40;Declaration of Helsinki&#41;&#46; The informed consent form was read and signed by the patients or their guardians before inclusion in the study&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Study procedures</span><p id="par0045" class="elsevierStylePara elsevierViewall">The participants were assessed at the time of inclusion in the study&#44; before starting radiotherapy&#44; and close to every five sessions &#40;with intervals ranging from three to seven sessions&#41; until the end of treatment&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">In the first evaluation&#44; demographic and clinical data&#44; breast cancer staging &#40;according to the American Joint Committee on Cancer &#8211; AJCC 8<span class="elsevierStyleSup">th</span> edition&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> radiotherapy regimen&#44; and photographs of the breasts before treatment were collected&#46; Subsequent evaluations included data on skin care&#44; direct observation of the irradiated site&#44; and photographs to assess the possible development of radiodermatitis&#46; At the beginning and during radiotherapy&#44; patients were instructed about treatment goals&#44; care for the irradiated area&#44; and adverse events&#46; Because it is an observational study&#44; there was no interference in the routine and prescriptions of the service&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Outcomes</span><p id="par0055" class="elsevierStylePara elsevierViewall">Primary outcome&#58; incidence of radiodermatitis during standard and booster treatment&#44; as well as degree of severity of the lesions&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Secondary outcomes&#58; i&#41; Factors associated with the development of radiodermatitis according to different classifications&#59; ii&#41; Time when radiodermatitis occurred during radiotherapy&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The diagnosis and classification of radiodermatitis in patients with breast cancer were performed according to criteria of the Radiation Therapy Oncology Group &#40;RTOG&#41;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#58; a&#41; Grade I&#44; mild erythema&#44; epilation&#44; and dry desquamation&#59; b&#41; Grade II&#44; painful erythema&#44; localized wet desquamation&#44; and moderate edema&#59; c&#41; Grade III&#44; confluent wet desquamation and significant edema&#59; or d&#41; Grade IV&#44; ulceration&#44; hemorrhage&#44; and necrosis&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Radiotherapy</span><p id="par0070" class="elsevierStylePara elsevierViewall">Radiotherapy was performed using the Eclipse&#8482; computerized treatment planning system &#40;versions 11&#46;0 and 13&#46;0&#41; from Varian Medical Systems&#46; The two-dimensional radiotherapy technique with a linear accelerator&#44; model Clinac&#174; 2100C&#44; by Varian&#44; was used&#46; The treatment was performed with X-ray beams &#40;photons&#41; of 6<span class="elsevierStyleHsp" style=""></span>MV with two or four tangent radiation fields&#46; Four radiation fields were used&#44; two with a wedge filter and two without the filter&#46; All patients were treated with the SSD &#40;Source Surface Distance&#41; technique&#44; in which the distance from the radiation source to the patient&#39;s skin is equal to the distance from the isocenter of the linear accelerator &#40;source distance<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>100&#46;0<span class="elsevierStyleHsp" style=""></span>cm&#41;&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Variables</span><p id="par0075" class="elsevierStylePara elsevierViewall">The information on the variables was collected by a single researcher and was obtained from the patient&#39;s medical records and through an interview guided by a data collection form prepared by the researchers&#46; Sociodemographic and clinical variables &#40;age&#44; ethnicity&#44; smoking status&#44; weight&#44; height&#44; body mass index&#44; comorbidities&#44; medications used&#41; related to radiotherapy and breast cancer and variables related to skin care were collected&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Statistical analysis</span><p id="par0080" class="elsevierStylePara elsevierViewall">Categorical variables were presented as percentages and continuous variables as means and standard deviations when parametric and as medians and first and third quartiles when non-parametric&#46; Due to the smaller number of patients with grades II to IV radiodermatitis&#44; patients were divided into two groups for comparison&#58; a&#41; Group 1&#44; patients with grade I radiodermatitis&#44; and b&#41; Group 2&#44; patients with grades II to IV radiodermatitis&#46; To compare clinical and demographic characteristics&#44; the chi-square or Fisher exact test were used for categorical variables&#44; the t-test for independent samples for continuous parametric variables&#44; and the Kruskal-Wallis test for non-parametric ones&#46; To assess risk factors for the development of higher degrees of radiodermatitis&#44; a multivariate logistic regression analysis was performed&#44; with variables with p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;1 being included in the model&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">To assess the risk of developing radiodermatitis as a function of the duration of treatment&#44; Cox proportional regression model was applied in the univariate and multivariate analyses&#44; and for the latter&#44; those with p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;1 were used in the univariate analysis&#46; The Kaplan-Meier analysis was used to plot the survival curve for the significant variables in the Cox model&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">All statistical analyses were performed using SPSS software&#44; version 23&#46;0 &#40;IBM&#41; and Epi Info&#8482; &#40;US Centers for Disease Control and Prevention&#41;&#46; P-values &#60; 0&#46;05 were considered significant&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><p id="par0095" class="elsevierStylePara elsevierViewall">A total of 122 women with breast cancer were admitted to the radiotherapy service from February to September 2017&#46; Nine patients were excluded&#58; four due to treatment with electron emission&#44; three due to skin changes secondary to the tumor&#44; and two due to limited mobility&#46; Therefore&#44; 113 patients remained in the study&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">The demographic&#44; clinical&#44; and radiotherapy characteristics of the 113 participants are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; The patients received standard radiotherapy&#44; totaling 9 to 30 sessions&#44; with a mean of 26 sessions &#40;SD<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;8&#41; and a mean dose of 5&#44;727&#46;4 &#40;SD<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4466&#46;1&#41; centigrays &#40;cGy&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">Of the 113 patients&#44; 68 &#40;60&#46;2&#37;&#41; also received booster treatment after completion of the standard radiotherapy&#44; with a mean radiation dose of 1&#44;202 &#40;SD<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>323&#46;2&#41; cGy&#46; The maximum dose on the skin ranged from 3&#37; to 11&#37; of the prescribed dose&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">In addition to radiotherapy performed on the breast topography&#44; 40 patients also received treatment with photon radiation on the ipsilateral supraclavicular fossa&#44; due to the presence of lymph node metastases&#46; It should be noted that because it is two-dimensional radiotherapy&#44; there was no irradiation to the lymph node chain of the internal mammary gland and axilla&#46;</p><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Primary outcome</span><p id="par0115" class="elsevierStylePara elsevierViewall">Some degree of radiodermatitis occurred in 111&#47;113 patients &#40;98&#46;2&#37;&#41;&#46; Regarding the severity&#44; 95&#47;113 patients &#40;85&#46;6&#37;&#41; developed grade I radiodermatitis&#44; 14&#47;113 &#40;12&#46;6&#37;&#41; grade II&#44; 1&#47;113 &#40;0&#46;9&#37;&#41; grade III&#44; and 1&#47;113 &#40;0&#46;9&#37;&#41; &#37;&#41; grade IV&#46; It is noteworthy that among the patients who received booster radiotherapy&#44; 54&#47;68 &#40;79&#46;4&#37;&#41; developed radiodermatitis during the standard radiotherapy and maintained grade I&#44; 12&#47;68 &#40;17&#46;6&#37;&#41; developed grade II&#44; and only six started the reaction after the booster treatment&#44; with 1&#47;68 &#40;1&#46;5&#37;&#41; developing grade III and 1&#47;68 &#40;1&#46;5&#37;&#41; grade IV and both started the reaction after the booster&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Figs&#46; 1</a> to <a class="elsevierStyleCrossRef" href="#fig0015">3</a> represent patients who developed different degrees of radiodermatitis in the breast&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">It is also important to highlight the characteristics of the two patients who did not develop any degree of radiodermatitis&#46; One was aged 77 years&#44; BMI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>25&#46;9&#59; received nine sessions&#44; with an average dose of 2400 cGy&#44; and did not continue the treatment due to her death&#46; The other patient&#44; 46 years old&#44; BMI of 28&#46;5&#44; received only 10 sessions as prescribed by the radiotherapist for palliative treatment&#44; also with an average dose of 2400 cGy&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Secondary outcomes</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Factors associated with radiodermatitis with higher severity degrees</span><p id="par0125" class="elsevierStylePara elsevierViewall">All variables depicted in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> were analyzed regarding their association with radiodermatitis of higher severity degrees &#40;II&#44; III and IV&#41;&#46; The variables in which the p-value in the univariate analysis was &#60; 0&#46;1 were included in the logistic regression&#59; therefore&#44; the following parameters were included&#58; body mass index&#44; diabetes mellitus&#44; dyslipidemia&#44; use of oral hypoglycemic agents&#44; analgesics and statins&#44; variation in radiation dose&#44; radiation depth&#44; irradiated volume&#44; and previous chemotherapy regimens&#46; This analysis showed that for each unit of Body Mass Index &#40;BMI&#41; increase&#44; the chance of occurrence of radiodermatitis grades II to IV increased by 14&#37; &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;14&#59; 95&#37; CI 1&#46;04&#8210;1&#46;26&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#41; and that the use of statins concomitantly with radiotherapy increased the risk by four-fold &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#46;27&#59; 95&#37; CI 1&#46;11&#8210;16&#46;42&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;035&#41;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The dose&#44; fractionation&#44; and energy received in the booster treatment for surgical scars were also evaluated&#46; In the statistical analysis&#44; these variables did not appear to be independent factors of radiodermatitis severity &#40;p<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;1&#41;&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Time of radiodermatitis onset</span><p id="par0135" class="elsevierStylePara elsevierViewall">The mean time for the appearance of radiodermatitis was 17<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5 &#40;range 5 to 27&#41; days&#46; In all cases&#44; radiodermatitis manifested before the completion of standard radiotherapy and starting booster radiotherapy&#46; It is noteworthy that 12&#47;113 &#40;10&#46;6&#37;&#41; patients received silicone prostheses and all developed grade I radiodermatitis&#44; with a mean time for onset of 18&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;7 &#40;variation of the time of onset of the reaction between 8 and 26&#41; days&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">All variables shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> were analyzed regarding their association with the time of onset of radiodermatitis&#46; Multivariate analysis&#44; performed using the Cox regression model&#44; showed that the exclusive use of hydrogel for skin hydration was an independent factor in delaying radiodermatitis onset when compared to patients using hydrogel associated with moisturizing creams &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#41;&#44; as shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; The median time for the appearance of skin lesions in patients using hydrogel alone was 19&#46;0 &#40;range 14&#46;5&#8210;23&#46;0&#41; days&#44; while for patients using hydrogel and moisturizing creams was 16&#46;0 &#40;range 13&#46;0 to 19&#46;0&#41; days &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#41;&#46; <a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>A shows the curve of patients free of radiodermatitis according to the skin hydration regimen used&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">Considering that the exclusive use of hydrogel delayed the onset of radiodermatitis by a few days&#44; a more detailed analysis of this group of patients was carried out&#44; which was divided according to the frequency of exclusive use of the hydrogel&#58; irregular &#40;less than once a day&#41;&#44; once or twice a day and more than twice a day&#46; The median time for the appearance of radiodermatitis in the last two groups that used the hydrogel more frequently was greater than in those with irregular use &#40;&#62; 2 times&#47;day&#58; 19&#46;0 &#91;17&#46;0&#8210;23&#46;0&#93; days&#59; 1&#8210; 2 times&#47;day&#58; 18&#46;0 &#91;14&#46;0&#8210;22&#46;0&#93; days&#59; irregular use&#58; 15&#46;0 &#91;13&#46;0&#8211;17&#46;0&#93; days&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;009&#41;&#46; <a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>B shows the curve of patients free of radiodermatitis according to the frequency of hydrogel used for skin hydration during the radiotherapy period&#46;</p></span></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0150" class="elsevierStylePara elsevierViewall">In the present study&#44; patients with breast cancer underwent two-dimensional radiotherapy with a linear accelerator and almost all of them &#40;98&#46;2&#37;&#41; had radiodermatitis in the breast&#59; this reaction usually started after a few sessions&#46; The only two patients who did not have radiodermatitis were those who received around 10 sessions&#44; therefore with a lower accumulated dose&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">These findings are very similar to those found by other studies with a high incidence rate of this toxicity&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;17</span></a> Yee et al&#46; conducted a systematic review including 96 randomized clinical trials with breast cancer patients who underwent external beam radiotherapy and found a variable incidence between studies from 26&#46;3&#37; to 92&#46;2&#37;&#46; They concluded that modes of radiotherapy administration such as Intensity-Modulated Radiotherapy &#40;IMRT&#41; and hypofractionation have been shown to decrease skin toxicity compared to conventional treatments&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">The study by Lee et al&#46; observed an incidence very similar to that of the present study&#44; with a 97&#46;3&#37; incidence of radiodermatitis in 111 women with breast cancer in South Korea&#59; however&#44; they did not report the radiotherapy technique used&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> A high rate of cutaneous toxicity was also observed in a Brazilian study&#44; carried out in a hospital in S&#227;o Paulo with 86 women&#44; in which 100&#37; of the patients developed this reaction after radiotherapy with a linear accelerator&#44; with a total dose of 5040 cGy &#40;180 cGy dose&#47;day&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> This high incidence corroborates the importance of studying radiodermatitis&#44; especially with regard to measures to prevent or delay its onset&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">A striking finding in this study was the impact of BMI on the incidence of higher degrees of radiodermatitis&#46; For each additional BMI unit&#44; there was a 14&#37; increase in the risk of grades II to IV skin reactions&#46; Other studies have also identified an association between BMI and an increased risk of radiodermatitis&#44; finding an association of BMI with the development of severe breast skin reactions&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> In another study&#44; Twardella et al&#46; also demonstrated an association between BMI and an increased risk of acute skin toxicity&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> These authors also identified a correlation between large breasts and higher BMI&#46; This finding could justify BMI as an independent risk factor for more severe radiodermatitis&#46; In a systematic review&#44; Mukesh et al&#46; found that greater breast volume was related to the risk of radiodermatitis&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Also&#44; it can be said that women with higher BMIs are likely to have larger breasts and&#44; consequently&#44; a greater risk of skin toxicity resulting from radiation&#46; The justification for these findings in larger breasts is due to the presence of extra tissue&#44; which interferes with radiation absorption because of non-homogeneous dose distribution and greater separation field&#46; There is also a greater drop of the breast into the mammary fold causing greater toxicities in this region&#59; this occurs because the redundant tissue in the inframammary region serves as a zone of accumulation of the photon beam dose&#44; which is then incident on the tissue opposite to it&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">Another finding in this study was the association between the continued use of statins and the development of more severe radiodermatitis&#46; This class of drugs increased the risk of patients experiencing grades II to IV skin toxicity by four-fold&#46; There is limited data in the literature confirming this association&#44; which has been described as radiation recall dermatitis &#40;RRD&#41;&#46; In this phenomenon&#44; the skin lesion appears after the end of radiotherapy&#46; It is best described for chemotherapy after radiotherapy&#46; However&#44; two cases of RRD with the use of statins have been reported in the literature&#46; Abadir &#38; Liebmann described the case of a patient with bladder cancer who received local radiotherapy and did not develop skin lesions during radiotherapy&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> However&#44; one year after the end of radiotherapy and beginning of the use of simvastatin for hypercholesterolemia&#44; the patient developed a lesion at the site of the previous irradiation&#46; A similar report was made by Taunk et al&#46;&#44; who described the case of a patient with breast cancer undergoing radiotherapy who developed radiodermatitis during treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> After five years&#44; the patient started using rosuvastatin and amlodipine to treat hypercholesterolemia and systemic arterial hypertension&#46; After two weeks&#44; she developed a skin lesion on the site where she had previously received irradiation consistent with radiodermatitis&#46; The question that arises is whether statins have any deleterious effects on the skin&#44; especially when associated with radiotherapy&#46; This class of drugs inhibits the enzyme 3-hydroxy-3-methylglutaryl coenzyme A &#40;HMG CoA&#41; reductase&#44; causing a significant reduction in serum cholesterol levels&#44; especially those of low-density lipoprotein cholesterol&#46; With this effect on HMG CoA reductase&#44; statins inhibit the mevalonate pathway and consequently reduce the production of non-steroidal isoprenoid compounds&#44; which results in pleiotropic cell effects including cell proliferation&#44; differentiation&#44; and myelination&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Reports of skin lesions induced by statin use have been presented&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23&#8211;26</span></a> Considering that radiation chemically damages the skin&#44; perhaps the use of statins can potentiate the damage in the skin regeneration process&#46; Another factor that should be mentioned&#44; although not evaluated in this study&#44; is drug interactions with statins&#44; which may increase the risk of side effects from these drugs&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Another important finding of this study was the use of hydrogel as a protective factor against radiodermatitis&#46; Although hydrogel use did not prevent the occurrence of radiodermatitis&#44; as only two participants did not have skin toxicity&#44; it delayed its onset when compared to patients who used hydrogel combined with moisturizing creams&#46; In the authors&#8217; service&#44; all patients undergoing radiotherapy are instructed to moisturize their skin three times a day&#44; either with moisturizer or hydrogel&#46; The recommendation of which product should be used for hydration depends on product accessibility for each patient&#46; As moisturizing creams were used as an alternative to hydrogel&#44; mainly due to the higher cost of hydrogel&#44; patients who used both products mostly belonged to the group who used hydrogel irregularly&#46; There was no group of patients who used only moisturizing cream on a regular basis&#44; making it impossible to draw more reliable conclusions about the best way to delay radiodermatitis&#46; The present study design&#44; as an observational one&#44; is not the best to evaluate the effectiveness of interventions&#46; To reduce confounding factors&#44; the appropriate study design is a clinical trial&#44; preferably randomized&#44; with the formation of standardized and more homogeneous treatment groups&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">However&#44; the use of hydrogel as a protective factor against radiodermatitis has already been demonstrated&#46; Censabella et al&#46; conducted a study comparing patients divided into a group that used hydrogel throughout radiotherapy &#40;preventive hydrogel group&#41; and two groups of matched historical controls&#58; one that applied dexpanthenol cream throughout therapy &#40;dexpanthenol group&#41; and one who applied dexpanthenol cream for 11&#8210;14 sessions of radiotherapy followed by hydro active gel &#40;curative hydrogel group&#41;&#46; The patients in the preventive hydrogel group developed less radiodermatitis and later than patients in the dexpanthenol group and did not differ from the curative hydrogel group&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Skin hydration is known to prevent skin toxicity from radiotherapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#44;29</span></a> Skin capacity to retain water is related to the outer stratum corneum of the epidermis<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> and it can be retained by hydration of corneocytes&#44; the cells that make up the stratum corneum&#46; The intracellular lipids in this layer form a transepidermal barrier that prevents water loss&#46; The sebaceous glands also play an important role in water retention&#44; mainly by producing glycerol&#46; When the skin is irradiated&#44; significant damage occurs&#44; affecting the production of glycerol and intracellular lipids&#44; allowing water loss and subsequent skin dryness&#44; which contributes to the effects of radiation on the skin and the development of radiodermatitis&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">In addition to the adverse events inherent to radiotherapy&#44; a Brazilian study showed that women who underwent radiotherapy for breast cancer had more frequent dermatological complaints&#44; which was statistically significant &#40;PR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;13&#59; 95&#37; CI 1&#46;03 to 1&#46;23&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;011&#41;&#46; These complaints were mainly related to radiodermatitis&#44; such as erythema&#44; hyperpigmentation&#44; xerosis&#44; and breast pruritus&#44; demonstrating the impact of these dermatological changes in patients being treated for breast cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">The main limitation of this study was its external validity&#46; The factors identified here should be considered for services and populations similar to those in the present study&#46; Radiotherapy in this sample was performed with planning based on flat images &#40;two-dimensional images&#41;&#46; Some services use a different radiotherapy technique with image-based volumetric planning &#40;three-dimensional&#41;&#46; Iwakawa et al&#46; previously demonstrated that the risk of skin reactions in the breast was highly dependent on the institution where the patient was treated&#44; due to different treatment techniques&#44; lack of dose homogeneity&#44; and the three-dimensional breast shape&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> For this reason&#44; this study was carried out to identify the characteristics of radiodermatitis with this type of radiotherapy&#46; Another limitation was not performing breast volumetry&#44; since larger breasts were identified in another study as an independent risk factor for greater radiodermatitis severity&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> However&#44; in the present study&#44; the irradiated volume was analyzed&#44; which is a variable related to breast volume&#44; but it did not appear to be an independent risk factor for severity and time of onset of radiodermatitis in the multivariate analysis&#46; Also&#44; the patients were not classified according to Fitzpatrick phototypes&#44; but according to the self-reported ethnicity&#44; showing a predominance of white ethnicity &#40;92&#46;1&#37;&#41; and this was not a factor related to the severity and time of onset of radiodermatitis&#46; The study by Twardella et al&#46;&#44; which classified patients according to phototype&#44; did not find this variable to be a risk factor&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Finally&#44; the findings of the present study are valid for radiotherapy with planning based on flat images&#44; two-dimensional radiotherapy technique with a linear accelerator&#44; and X-ray beams &#40;photons&#41;&#44; with a mean dose of 5&#44;727 cGy&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conclusion</span><p id="par0205" class="elsevierStylePara elsevierViewall">The present study contributes to a better understanding of radiodermatitis in women with breast cancer&#44; as it shows its high incidence&#44; the relationship of its severity with BMI and the use of statins&#44; and the protective effect of hydrogel use&#46; Future studies are required to increase knowledge about the factors associated with radiodermatitis&#44; considering different populations and the diversity of treatments&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Financial support</span><p id="par0210" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Authors&#39; contributions</span><p id="par0215" class="elsevierStylePara elsevierViewall">Loren Giagio Cavalcante&#58; Design and planning of the study&#59; drafting and editing of the manuscript&#44; collection&#44; analysis&#44; and interpretation of data&#59; literature review&#59; critical review of the manuscript&#59; approval of the final version of the manuscript&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Rejane Aparecida Rodrigues Domingues&#58; Data collection&#59; literature review&#59; critical review of the manuscript&#59; approval of the final version of the manuscript&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">Batista de Oliveira Junior&#58; Analysis and interpretation of data&#59; critical review of the manuscript&#59; approval of the final version of the manuscript&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">Marco Ant&#244;nio Rodrigues Fernandes&#58; Analysis and interpretation of data&#59; critical review of the manuscript&#59; approval of the final version of the manuscript&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Eduardo Carvalho Pessoa&#58; Analysis and interpretation of data&#59; critical review of the manuscript&#59; approval of the final version of the manuscript</p><p id="par0240" class="elsevierStylePara elsevierViewall">Luciana Patr&#237;cia Fernandes Abbade&#58; Effective participation in research orientation&#59; analysis and interpretation of data&#59; statistical analysis&#59; drafting and editing of the manuscript&#59; literature review&#59; critical review of the manuscript&#59; approval of the final version of the manuscript&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflicts of interest</span><p id="par0245" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
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                  "identificador" => "sec0060"
                  "titulo" => "Factors associated with radiodermatitis with higher severity degrees"
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                  "identificador" => "sec0065"
                  "titulo" => "Time of radiodermatitis onset"
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          "titulo" => "Discussion"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2022-11-30"
    "fechaAceptado" => "2023-01-10"
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        0 => array:4 [
          "clase" => "keyword"
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          "palabras" => array:4 [
            0 => "Breast neoplasm"
            1 => "Radiodermatitis"
            2 => "Radiotherapy&#44; adjuvant"
            3 => "Risk factors"
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    "resumen" => array:1 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">One of the main adverse reactions of adjuvant radiotherapy for breast cancer is radiodermatitis&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">To assess the incidence of radiodermatitis in women with breast cancer&#44; identify factors associated with its severity and determine the time at which this event occurs&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Prospective cohort study in 113 women with breast cancer who were evaluated before radiotherapy and at every fifth session until the end of treatment&#46; Logistic regression and Cox proportional regression model were used for the assessment of risk factors&#59; P values &#60; 0&#46;05 were considered significant&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">The incidence rate of radiodermatitis was 98&#46;2&#37; and it was demonstrated that for each additional point of the Body Mass Index &#40;BMI&#41;&#44; the chance of occurrence of grades II to IV radiodermatitis increases by 14&#37; &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;14 &#91;95&#37; CI 1&#46;04&#8211;1&#46;26&#93;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#41; and statin use increases the risk of more severe skin lesions by four-fold &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#46;27 &#91;95&#37; CI 1&#46;11&#8211;16&#46;42&#93;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;035&#41;&#46; The exclusive use of hydrogel for skin hydration was an independent factor in delaying the onset of radiodermatitis &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;55 &#91;95&#37; CI 0&#46;36&#8211;0&#46;82&#93;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Study limitations</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">The main limitation of this study was its external validity&#46; The identified factors should be considered for services and populations similar to those in this study&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclusions</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">There was a high incidence of radiodermatitis and its severity was related to higher BMI&#44; statin use&#59; there was a protective effect of hydrogel use&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Study conducted at the Department of Infectology&#44; Dermatology&#44; Diagnostic Imaging and Radiotherapy&#44; Faculdade de Medicina&#44; Universidade Estadual Paulista&#44; Botucatu&#44; SP&#44; Brazil&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Images of the breast submitted to radiotherapy&#46; &#40;A&#41; Before the first radiotherapy session&#46; &#40;B&#41; After 28 sessions of radiotherapy with a total dose of 5271 cGy &#8211; grade I radiodermatitis is observed&#44; characterized by mild erythema and hyperpigmentation&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Images of the breast submitted to radiotherapy&#46; &#40;A&#41; Before the first radiotherapy session&#46; &#40;B&#41; After 28 radiotherapy sessions with a total dose of 5221 cGy &#8211; grade II radiodermatitis is observed&#44; characterized by intense and painful erythema and moderate nipple edema&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Images of the inframammary fold after 28 radiotherapy sessions with a total dose of 5654 cGy&#46; &#40;A&#41; Grade II radiodermatitis&#44; characterized by localized exulceration &#40;moist desquamation&#41;&#46; &#40;B&#41; Fourteen days after the end of radiotherapy shows grade IV radiodermatitis&#44; characterized by ulceration&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Value&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">57&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Tumor staging&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">White women&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">104 &#40;92&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>I&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8804; 4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">38 &#40;33&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>II&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">44 &#40;40&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>5&#8211;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27 &#40;23&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;27&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>9&#8211;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22 &#40;19&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">03 &#40;2&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8805; 12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26 &#40;23&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Previous chemotherapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Smoking&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;12&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Not performed&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 &#40;21&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Body Mass Index &#40;kg&#47;m&#178;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>DCT<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">69 &#40;61&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Comorbidities&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Other regimens <a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 &#40;17&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Diabetes mellitus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 &#40;21&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Therapy with tamoxifen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36 &#40;31&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Arterial hypertension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66 &#40;58&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Therapy with anastrozole&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43 &#40;38&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Heart&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">09 &#40;8&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Performed surgery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dyslipidemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;11&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mastectomy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18 &#40;15&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hypothyroidism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;13&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Adenectomy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;8&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Drugs for continuous use&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Setorectomy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">81 &#40;71&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hypoglycemic agents&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 &#40;21&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Radiation dose &#40;cGy&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;727&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;466&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Anti-hypertensive drugs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63 &#40;55&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose variation &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Analgesics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">08 &#40;7&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Radiated field &#40;cm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Thyroid drugs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;13&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Depth&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Statins&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;12&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Height&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Vitamins&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 &#40;22&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Length&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tumor histopathology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Radiated volume &#40;cm<span class="elsevierStyleSup">3</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;633&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>869&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Carcinoma <span class="elsevierStyleItalic">in situ</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">06 &#40;5&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Skin hydration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Invasive carcinoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">99 &#40;87&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hydrogel only&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50 &#40;44&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Lobular carcinoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">05 &#40;4&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hydrogel with moisturizer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63 &#40;55&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Special carcinoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">03 &#40;2&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mean oral hydration &#40;L&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "identificador" => "tblfn0010"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Demographic&#44; clinical&#44; and therapeutic characteristics of 113 women with breast cancer submitted to photon radiation therapy&#46;</p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vitamin supplementation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;68 &#40;0&#46;40 &#8211; 1&#46;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Previous chemotherapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>DCT regimen &#40;reference&#41;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8210;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8210;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Other regimens<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;50 &#40;0&#46;89 &#8211; 2&#46;52&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Not performed&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;03 &#40;0&#46;60 &#8211; 1&#46;76&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hydrogel use <span class="elsevierStyleItalic">vs&#46;</span> hydrogel with moisturizer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;55 &#40;0&#46;36 &#8211; 0&#46; 82&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab3426404.png"
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            0 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">DCT regimen&#8211; Doxorubicin&#44; Cyclophosphamide and Taxane&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0020"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Other regimens &#8211; Cyclophosphamide plus taxane&#44; Doxorubicin plus cyclophosphamide&#44; Doxorubicin&#44; cyclophosphamide and carboplatin&#44; Doxorubicin&#44; cyclophosphamide and fluorouracil&#44; Taxane plus carboplatin&#46;</p>"
            ]
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Multivariate analysis of predictive factors for time to radiodermatitis onset in women with breast cancer treated by photon radiation therapy&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:32 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Postoperative radiotherapy after breast-conserving surgery for early-stage breast cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "C&#46; Speers"
                            1 => "L&#46;J&#46; Pierce"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jamaoncol.2015.5805"
                      "Revista" => array:5 [
                        "tituloSerie" => "JAMA Oncol&#46;"
                        "fecha" => "2016"
                        "volumen" => "2"
                        "paginaInicial" => "1075"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27243924"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality&#58; meta-analysis of individual patient data for 8135 women in 22 randomised trials"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [
                            0 => "EBCTCG &#40;Early Breast Cancer Trialists&#8217; Collaborative Group&#41;"
                            1 => "P&#46; McGale"
                            2 => "C&#46; Taylor"
                            3 => "D&#46; Correa"
                            4 => "D&#46; Cutter"
                            5 => "F&#46; Duane"
                            6 => "M&#46; Ewertz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(14)60488-8"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet&#46;"
                        "fecha" => "2014"
                        "volumen" => "383"
                        "paginaInicial" => "2127"
                        "paginaFinal" => "2135"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24656685"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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