Radiation-induced Skin Toxicity Research Articles

A dosiomics model for prediction of radiation-induced acute skin toxicity in breast cancer patients: machine learning-based study for a closed bore linac

BackgroundRadiation induced acute skin toxicity (AST) is considered as a common side effect of breast radiation therapy. The goal of this study was to design dosiomics-based machine learning (ML) models for prediction of AST, to enable creating optimized treatment plans for high-risk individuals.MethodsDosiomics features extracted using Pyradiomics tool (v3.0.1), along with treatment plan-derived dose volume histograms (DVHs), and patient-specific treatment-related (PTR) data of breast cancer patients were used for modeling. Clinical scoring was done using the Common Terminology Criteria for Adverse Events (CTCAE) V4.0 criteria for skin-specific symptoms. The 52 breast cancer patients were grouped into AST 2 + (CTCAE ≥ 2) and AST 2 − (CTCAE < 2) toxicity grades to facilitate AST modeling. They were randomly divided into training (70%) and testing (30%) cohorts. Multiple prediction models were assessed through multivariate analysis, incorporating different combinations of feature groups (dosiomics, DVH, and PTR) individually and collectively. In total, seven unique combinations, along with seven classification algorithms, were considered after feature selection. The performance of each model was evaluated on the test group using the area under the receiver operating characteristic curve (AUC) and f1-score. Accuracy, precision, and recall of each model were also studied. Statistical analysis involved features differences between AST 2 − and AST 2 + groups and cutoff value calculations.ResultsResults showed that 44% of the patients developed AST 2 + after Tomotherapy. The dosiomics (DOS) model, developed using dosiomics features, exhibited a noteworthy improvement in AUC (up to 0.78), when spatial information is preserved in the dose distribution, compared to DVH features (up to 0.71). Furthermore, a baseline ML model created using only PTR features for comparison with DOS models showed the significance of dosiomics in early AST prediction. By employing the Extra Tree (ET) classifiers, the DOS + DVH + PTR model achieved a statistically significant improved performance in terms of AUC (0.83; 95% CI 0.71–0.90), accuracy (0.70), precision (0.74) and sensitivity (0.72) compared to other models.ConclusionsThis study confirmed the benefit of dosiomics-based ML in the prediction of AST. However, the combination of dosiomics, DVH, and PTR yields significant improvement in AST prediction. The results of this study provide the opportunity for timely interventions to prevent the occurrence of radiation induced AST.

Optimizing dosage in linear accelerator based on predictive analysis of radiation induced skin toxicity using machine learning techniques

Optimizing dosage in linear accelerator based on predictive analysis of radiation induced skin toxicity using machine learning techniques

Genetic landscape of breast cancer subtypes following radiation therapy: insights from comprehensive profiling.

In breast cancer, in the era of precision cancer therapy, different patterns of genetic mutations dictate different treatments options. However, it is not clear whether the genetic profiling of breast cancer patients undergoing breast-conserving surgery is related to the adverse reactions caused by radiotherapy. We collected formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 54 breast cancer patients treated with radiation after breast-conserving surgery and identified comprehensive molecular information in hundreds of cancer-associated genes by FoundationOne CDx (F1CDx), a next-generation sequencing (NGS)-based assay. Among our cohort of 54 breast cancer patients, we found high-frequency mutations in cancer-related genes such as TP53 (56%), RAD21 (39%), PIK3CA (35%), ERBB2 (24%), and MYC (22%). Strikingly, we detected that the WNT pathway appears to be a signaling pathway with specific high-frequency mutations in the HER2 subtype. We also compared the mutation frequencies of the two groups of patients with and without cutaneous radiation injury (CRI) after radiotherapy and found that the mutation frequencies of two genes, FGFR1 and KLHL6, were significantly higher in patients with CRI : No subgroup than in those with CRI : Yes. Different breast cancer subtypes have their own type-specific mutation patterns. FGFR1 and KLHL6 mutations are protective factors for radiation-induced skin toxicity in breast cancer patients.

Do Barrier Films Impact Long-Term Skin Toxicity following Whole-Breast Irradiation? Objective Follow-Up of Two Randomised Trials.

Purpose: Hydrofilm, a polyurethane-based barrier film, can be used to prevent acute radiation dermatitis (RD) in adjuvant whole-breast irradiation (WBI) for breast cancer. This cost-effective prophylactic measure is currently being recommended to a growing number of patients, yet long-term safety data and its impact on late radiation-induced skin toxicity such as pigmentation changes and fibrosis have not been investigated. Methods: We objectively evaluated patients who were previously enrolled in either of two intrapatient-randomised (lateral versus medial breast halve) controlled trials on the use of Hydrofilm for RD prevention (DRKS00029665; registered on 19 July 2022). Results: Sixty-two patients (47.7% of the initial combined sample size) provided consent for this post-hoc examination, with a median follow-up time (range) of 58 (37-73) months. Following WBI, there was a significant increase in yellow skin tones of the entire breast when compared to baseline measurements before WBI (p < 0.001) and a significant increase of cutis, subcutis, and oedema thickness (p < 0.001, p < 0.001, and p = 0.004, respectively). At follow-up, there were no significant differences in either pigmentation changes or skin fibrosis between the Hydrofilm and standard of care breast halves. Conclusion: These data suggest that Hydrofilm can be safely used in the context of acute RD prevention, without affecting late side effects, supporting its widespread use.

Non-invasive physical plasma for preventing radiation dermatitis in breast cancer: Results from an intrapatient-randomised double-blind placebo-controlled trial

Background and PurposeTo investigate the effect of topical non-invasive physical plasma (NIPP), a volatile mix generated out of ambient air, on prevention of acute radiation dermatitis (RD) during and after whole-breast irradiation (WBI). Materials and MethodsLateral and medial breast halves were randomised within each patient to receive either 120 s of NIPP or sham treatment daily during WBI. Standard skin care with urea lotion was applied to the whole breast. Blinded acute skin toxicity was assessed weekly for each breast half separately and included clinician- (CTCAE) and patient-reported (modified RISRAS), and objective (spectrophotometry) assessments. As an additional external control, a comparable standard of care (SoC) patient collective from a previous prospective trial was used. ResultsSixty-four patients were included. There were no significant differences between breast halves. Post-hoc comparison with a similar SoC control collective revealed OR = 0.28 (95% CI 0.11–0.76; p = 0.014) for grade ≥ 2 RD upon WBI completion, along with less hyperpigmentation (p < 0.001), oedema (p = 0.020), dry (p < 0.001) and moist desquamation (p = 0.017), pain, itching, and burning (p < 0.001 for each). Tolerability of NIPP was excellent and side effects were not observed. ConclusionEven though there were no differences between intrapatient-randomised breast halves, the overall incidence and severity of acute radiation-induced skin toxicity were considerably lower when compared to a prospectively collected SoC cohort. Our data suggest the potential benefit of NIPP in RD prevention. A randomised trial with a physical control group is warranted to confirm these promising results (DRKS00026225).

Characterization of Objective Skin Color Changes during and after Breast and Chest Wall Radiotherapy and Correlation with Radiation-Induced Skin Toxicity in Breast Cancer Patients, Including Patients with Skin of Color

Radiation dermatitis (RD) is common among women undergoing breast and chest wall radiotherapy (RT); however, existing scales to assess the severity of RD are subjective and do not account for variability in skin of color (SOC). For instance, the Common Terminology Criteria for Adverse Events (CTCAE) criteria do not include hyperpigmentation in the grading scale. There is data indicating worse RD in African American and Hispanic patients; however, the rate and severity in SOC remains unknown given the lack of data using objective measures of RD. Spectrophotometry is one method to quantify the appearance of color by measuring spectral characteristics without the bias associated with subjective clinical scoring. We present a phase I prospective non-therapeutic clinical trial to objectively define SOC at baseline and evaluate spectrophotometric skin changes during and after breast or chest wall RT in parallel with physician-graded RD using CTCAE criteria. We hypothesize that there will be greater discrepancy between physician graded RD and objective measures of RD in patients with SOC in whom hyperpigmentation will be undercaptured by physician-grading. This is the first study intending to correlate SOC with objective changes after RT as a reliable indicator of RD. We offer a novel system for evaluating RD that is applicable to SOC. A total of 60 patients with localized breast cancer (stage 0-III) undergoing conventional whole breast or chest wall RT (50Gy/ 25 fx), hypofractionated whole breast RT (40.5Gy/15 fx) or ultrahypofractionated partial breast RT (6Gy x5), with or without regional nodal RT were enrolled. 3 skin color readouts using the Commission International de l'Eclairage 3D color system (l*, a*, b*) were measured within the radiation field using a spectrophotometer at baseline, once weekly during RT, 10 days post RT, 4 weeks and 12 months post RT. The spectrophotometer is a non-invasive, hand-held device that is used in the clinic room with no additional equipment or setup requirements. Data is automatically exported to a spreadsheet organized by timepoint and patient. The l* axis is a gray scale (0 = black, 100 = white) correlating with skin pigmentation and the a* axis describes red and green values correlating with erythema. The primary objective is to evaluate the changes from baseline in skin color readouts in the quadrant of tumor location during and after RT based on fractionation. The secondary objective is to evaluate changes within and across groups defined by baseline skin color. Exploratory objectives include evaluating the association of baseline color readouts and changes after RT with acute and late grade > 2 clinician-rated skin and subcutaneous tissue effects according to the CTCAE, v5.0, physician graded cosmesis and clinical interventions to treat RD, such as use of topical steroids and oral analgesics. As of January 2023, we have enrolled 100% of the planned patients. To be determined. To be determined. Clinical Study Identifier: S22-00192.

Surface Dose and Skin Toxicity Analysis in Breast Cancer Radiotherapy after Conserving Surgery with Five Treatment Modalities

The present study aimed to evaluate surface dose and skin toxicity in breast cancer after breast-conserving surgery with five treatment modalities: flattening filter mode of intensity modulated radiation therapy (IMRT-FF,6MV), flattening filter-free mode of intensity modulated radiation therapy (IMRT-FFF,6MV), direct mode of TOMO (TOMO-direct, FFF, 6MV), helical mode of TOMO (TOMO-helical, FFF, 6MV), intensity modulated proton therapy (IMPT, spot scanning). Ten patients with breast cancer treated at our institution after breast-conserving surgery were randomly selected for this study. Five plans were designed for each patient with the same target coverage and the prescription of 50Gy/25f, IMRT-6FF, IMRT-6FFF, TOMO-direct, TOMO-helical, and IMPT. Based on CT datasets, IMRT-6FFF, TOMO-direct, TOMO-helical, and IMPT were compared to IMRT-6FF with skin dose and skin toxicity. Among the five plannings, the angles of the IMRT-6FF vs. IMRT-6FFF and TOMO-direct were the same. We extracted the relative complement in the Body of its 3Derosion defined by a spherical structuring element of radius r = 3 mm and r = 5mm (skin3 and skin5). To calculate the relative Dose-surface histograms (DSH), we used the surface of patients receiving at least 5Gy to delimit the breast region's skin area and normalize the absolute DSH. Skin dose were assessed with V5Gy, V10Gy, V15Gy, V20Gy, V25Gy, V30Gy, V40Gy, V45Gy, V50Gy of the structure of skin3 and skin5. The published NTCP LKB (normal tissue complication probability, Lyman-Kutcher-Burman) model (TD50 = 39 Gy,m = 0.14,n = 0.38) was employed to evaluate severe acute radiation-induced skin toxicity. There was no statistically significant difference between the structure of skin3 and skin5 between IMRT-6FF and IMRT-6FFF. For the same PTV coverage, the TOMO-helical plans had significantly higher surface dose in terms of V5Gy, V10Gy, and V15Gy than the IMRT plans (p <0.005). For structure of skin3, mean V30Gy, V35Gy, V40Gy, V45Gy, V50Gy were (64.0%,65.8%,79.0%,70.0%,64.6%), (51.3%,55.4%,74.3%,61.7%,59.5%), (32.4%,36.6%,65.2%,53.0%,53.0%), (13.7%,14.1%,45.8%,35.7%,37.6%), (1.6%/0.8%/12.2%,6.6%,1.0%). For the structure of skin5, mean V30Gy, V35Gy, V40Gy, V45Gy, V50Gy were (66.1%,67.1%,76.4%,68.6%,62.6%), (57.9%,60.4%,72.3%,61.2%,57.7%), (45.5%,48.4%,65.2%,53.9%,51.8%), (28.4%,30.8%,51.2%,42.0%,40.0%), (6.8%,6.3%,22.6%,17.9%,8.0%).Compared to IMRT-6FF, TOMO-direct and TOMO-helical had higher surface dose(p<0.05). For IMRT-6FF/IMRT-6FFF/TOMO-direct/TOMO-helical/IMPT, the mean ratio of severe acute radiational skin toxicity were14.7%,17.1%,46.3%,29.4%, and 24.1%. For TOMO-direct and TOMO-helical planning, the skin dose and toxicity ratio were higher than IMRT-6FF. Compared to IMRT-6FF, V45Gy of skin3 and V40Gy of skin5 of IMPT were higher than IMRT-6FF, while the skin toxicity ratio was no significant difference.

Risk of Radiation Dermatitis in Patients With Skin of Color Who Undergo Radiation to the Breast or Chest Wall With and Without Regional Nodal Irradiation

Acute radiation dermatitis (ARD) is common after radiation therapy for breast cancer, with data indicating that ARD may disproportionately affect Black or African American (AA) patients. We evaluated the effect of skin of color (SOC) on physician-reported ARD in patients treated with radiation therapy. We identified patients treated with whole breast or chest wall ± regional nodal irradiation or high tangents using 50 Gy in 25 fractions from 2015 to 2018. Baseline skin pigmentation was assessed using the Fitzpatrick scale (I=light/pale white to VI=black/very dark brown) with SOC defined as Fitzpatrick scale IV to VI. We evaluated associations among SOC, physician-reported ARD, late hyperpigmentation, and use of oral and topical treatments for RD using multivariable models. A total of 325 patients met eligibility, of which 40% had SOC (n=129). On multivariable analysis, Black/AA race and chest wall irradiation had a lower odds of physician-reported grade 2 or 3 ARD (odds ratio [OR], 0.110; 95% confidence interval [CI], 0.030-0.397; P=.001; OR, 0.377; 95% CI, 0.161-0.883; P=.025), whereas skin bolus (OR, 8.029; 95% CI, 3.655-17.635; P=0) and planning target volume D0.03cc (OR, 1.001; 95% CI, 1.000-1.001; P=.028) were associated with increased odds. On multivariable analysis, SOC (OR, 3.658; 95% CI, 1.236-10.830; P=.019) and skin bolus (OR, 26.786; 95% CI, 4.235-169.432; P=0) were associated with increased odds of physician-reported late grade 2 or 3 hyperpigmentation. There was less frequent use of topical steroids to treat ARD and more frequent use of oral analgesics in SOC versus non-SOC patients (43% vs 63%, P < .001; 50% vs 38%, P=.05, respectively). Black/AA patients exhibited lower odds of physician-reported ARD. However, we found higher odds of late hyperpigmentation in SOC patients, independent of self-reported race. These findings suggest that ARD may be underdiagnosed in SOC when using the physician-rated scale despite this late evidence of radiation-induced skin toxicity.

Radiobiological modelling of radiation-induced acute skin toxicity (dermatitis): A single institutional study of breast carcinoma.

The purpose of the study was to estimate the fitting parameters of the sigmoidal dose response (SDR) curve of radiation-induced acute dermatitis in breast cancer patients treated with intensity-modulated radiation therapy for calculation of normal tissue complication probability (NTCP). Twenty-five breast cancer patients were enrolled to model the SDR curve for acute dermatitis. The acute radiation-induced (ARI) dermatitis toxicity was assessed weekly for all the patients, and their scores were determined using the common terminology criterion adverse events version 5.0. The radiobiological parameters n, m, TD50, and γ50 were derived using the fitted SDR curve obtained from breast cancer Patient's clinical data. ARI dermatitis toxicity in carcinoma of breast patients was calculated for the end point of acute dermatitis. The n, m, TD50, and γ50 parameters from the SDR curve of Grade-1 dermatitis are found to be 0.03, 0.04, 28.65 ± 1.43 (confidence interval [CI] 95%) and 1.02 and for Grade-2 dermatitis are found to be 0.026, 0.028, 38.65 ± 1.93 (CI. 95%) and 1.01 respectively. This research presents the fitting parameters for NTCP calculation of Grade-1 and Grade-2 acute radiation-induced skin toxicity in breast cancer for the dermatitis end point. The presented nomograms of volume versus complication probability and dose versus complication probability assist radiation oncologists in establishing the limiting dose to reduce acute toxicities for different grades of acute dermatitis in breast cancer patients.

Prediction of radiation-induced acute skin toxicity in breast cancer patients using data encapsulation screening and dose-gradient-based multi-region radiomics technique: A multicenter study.

Radiation-induced dermatitis is one of the most common side effects for breast cancer patients treated with radiation therapy (RT). Acute complications can have a considerable impact on tumor control and quality of life for breast cancer patients. In this study, we aimed to develop a novel quantitative high-accuracy machine learning tool for prediction of radiation-induced dermatitis (grade ≥ 2) (RD 2+) before RT by using data encapsulation screening and multi-region dose-gradient-based radiomics techniques, based on the pre-treatment planning computed tomography (CT) images, clinical and dosimetric information of breast cancer patients. 214 patients with breast cancer who underwent RT between 2018 and 2021 were retrospectively collected from 3 cancer centers in China. The CT images, as well as the clinical and dosimetric information of patients were retrieved from the medical records. 3 PTV dose related ROIs, including irradiation volume covered by 100%, 105%, and 108% of prescribed dose, combined with 3 skin dose-related ROIs, including irradiation volume covered by 20-Gy, 30-Gy, 40-Gy isodose lines within skin, were contoured for radiomics feature extraction. A total of 4280 radiomics features were extracted from all 6 ROIs. Meanwhile, 29 clinical and dosimetric characteristics were included in the data analysis. A data encapsulation screening algorithm was applied for data cleaning. Multiple-variable logistic regression and 5-fold-cross-validation gradient boosting decision tree (GBDT) were employed for modeling training and validation, which was evaluated by using receiver operating characteristic analysis. The best predictors for symptomatic RD 2+ were the combination of 20 radiomics features, 8 clinical and dosimetric variables, achieving an area under the curve (AUC) of 0.998 [95% CI: 0.996-1.0] and an AUC of 0.911 [95% CI: 0.838-0.983] in the training and validation dataset, respectively, in the 5-fold-cross-validation GBDT model. Meanwhile, the top 12 most important characteristics as well as their corresponding importance measures for RD 2+ prediction in the GBDT machine learning process were identified and calculated. A novel multi-region dose-gradient-based GBDT machine learning framework with a random forest based data encapsulation screening method integrated can achieve a high-accuracy prediction of acute RD 2+ in breast cancer patients.

Topical natural-origin polynucleotides in radiation-induced skin and mucosal toxicity.

Seventy to 90 percent of patients who have received radiation treatment struggle with radiation skin and mucosal toxicity. The inflicted damage to progenitor cells and local microcirculation makes it more likely that wounds, infections, and fibrosis may occur; lesions of variable severity often co-exist. Acute erythema, hyperpigmentation, and mild desquamation usually wane in weeks and require only minor treatment. Conversely, the management of persistent radiation dermatitis and telangiectasia remains unsatisfactory; chronic lesions may progress to tissue atrophy and disfiguring fibrosis.

Surface Dose and Skin Toxicity in Low-Magnetic Field MR-Linac

<h3>Purpose/Objective(s)</h3> Radiation induced skin toxicity is a common side effect that results in poor patient satisfaction and unplanned treatment breaks thus prolonging the overall treatment time with poor outcome. It is hypothesized that treatments on low-field MR-Linac will not produce higher surface dose which is investigated in this study. <h3>Materials/Methods</h3> Skin dose has always been an area of active clinical interest that is dependent on many parameters including beam energy, field size, material thickness and atomic number in the beam, material distance from surface, source to surface distance, beam angle (obliquity factor), concomitant chemotherapy etc. Along with these parameters, magnetic field is also a critical parameter that affect surface dose. With the development of the MRL system focus has shifted towards Lawrence force giving rise to electron return effect along with other treatment parameters affecting the skin dose. A Linac equipped with 6MV FFF photons with 90 cm source to axis distance is used. A Markus parallel plate ionization chamber is used in a solid water phantom with proper correction factor to investigate surface and buildup dose with six different gantry angles 15⁰ apart gantry (equivalent of standard Linac 0⁰, 15⁰, 30⁰, 45⁰, 60⁰, and 75⁰) for field sizes of 1.66 × 1.66 cm² (small), 9.96 × 9.9 cm² (reference) and 24.1 × 24.1 cm² (maximum). Measurements were made with increasing buildup thickness in steps of 1 mm to 20 mm of solid water in 0.35 T magnetic field. <h3>Results</h3> In traditional linear accelerators surface dose is 30-40% for a 6MV photon beam, without any modifier. This value increases significantly with beam angle. In MR-Linac, surface dose is relatively low, 12.6%, 14.9% and 16.7% for small, reference and maximum fields at zero-degree gantry angle, respectively. These values are 12% to 2% higher (at 0⁰ and 75⁰ respectively) for maximum field size compared to the reference field size. For lower field sizes minimum variation of 10% was observed at 75° for reference field size. The surface dose increases with increasing radiation field size but magnitude is still lower as the case with traditional lilacs. Table 1 shows the surface dose with field size and gantry angles. <h3>Conclusion</h3> Surface dose in low-field magnetic environment is relatively lower than traditional accelerators. It is concluded that low-field MR-Linac system may not add any additional skin toxicity compared to conventional Linac. However, the effect may be different for high-field MR-Linac system, and appropriate skin evaluation needs to be performed to differentiate between radiation induced toxicity specially for the oblique beams versus RF-thermal effect.

Factors on development and severity of acute radiodermatitis: prospective single-center study

Aim: Although prior literature has examined the treatment and patient-associated factors affecting the development and severity of acute radiodermatitis, there are relatively few prospective studies evaluating both. This study was prospectively designed to evaluate factors affecting the development and extent of radiation-induced acute skin toxicity called radiodermatitis (RD). &#x0D; Material and Method: A total of 63 patients who underwent radiotherapy (RT) in Ankara Atatürk Research and Education Hospital between July 2017 and October 2018 were evaluated. Patients’ demographic status, disease/treatment details, hemoglobin, ferritin, folic acid, Vit B12, and hemoglobin A1c values were recorded. The development and grade of RD were evaluated weekly by the same radiation oncologist using the Radiation Therapy Oncology Group (RTOG) radiation toxicity guideline.&#x0D; Results: There was no significant relationship between the development of any degree of RD and gender, concomitant chemotherapy (CT), pre-RT CT, comorbid disease, RT technique and blood parameters (Hb, Hba1c, ferritin, folic acid and B12). The development of grade 2-3 RD was significantly affected by the number of operations (p=0.032) and total dose of RT (p=0.008). In patients with grade 2/3 RD, the RT dose at which RD first appeared was 20 Gy (range, 14-36); in patients with grade 1 RD, this value was 32 Gy (range, 16-56) (p=0.018).&#x0D; Conclusion: There is no significant relationship between the development of acute radiodermatitis and Hba1c, hemoglobin, ferritin, B12 and folic acid levels. There was a significant correlation between grade of RD and repeated surgery, increase in total RT dose and early onset of RD.

Quantitative assessments of late radiation-induced skin and soft tissue toxicity and correlation with RTOG scales and biological equivalent dose in breast cancer

PurposeRadiation-induced toxicity (RIT) is usually assessed by inspection and palpation. Due to their subjective and unquantitative nature, objective methods are required. This study aimed to determine whether a quantitative tool is able to assess RIT and establish an underlying BED-response relationship in breast cancer.MethodsPatients following seven different breast radiation protocols were recruited to this study for RIT assessment with qualitative and quantitative examination. The biologically equivalent dose (BED) was used to directly compare different radiation regimens. RIT was subjectively evaluated by physicians using the Radiation Therapy Oncology Group (RTOG) late toxicity scores. Simultaneously an objective multiprobe device was also used to quantitatively assess late RIT in terms of erythema, hyperpigmentation, elasticity and skin hydration.ResultsIn 194 patients, in terms of the objective measurements, treated breasts showed higher erythema and hyperpigmentation and lower elasticity and hydration than untreated breasts (p < 0.001, p < 0.001, p < 0.001, p = 0.019, respectively). As the BED increased, Δerythema and Δpigmentation gradually increased as well (p = 0.006 and p = 0.002, respectively). Regarding the clinical assessment, the increase in BED resulted in a higher RTOG toxicity grade (p < 0.001). Quantitative assessments were consistent with RTOG scores. As the RTOG toxicity grade increased, the erythema and pigmentation values increased, and the elasticity index decreased (p < 0.001, p = 0.016, p = 0.005, respectively).ConclusionsThe multiprobe device can be a sensitive and simple tool for research purpose and quantitatively assessing RIT in patients undergoing radiotherapy for breast cancer. Physician-assessed toxicity scores and objective measurements revealed that the BED was positively associated with the severity of RIT.

Targeted Next-Generation Sequencing for the Identification of Genetic Predictors of Radiation-Induced Late Skin Toxicity in Breast Cancer Patients: A Preliminary Study.

Normal tissue radiosensitivity is thought to be influenced by an individual’s genetic background. However, the specific genetic variants underlying the risk of late skin reactions following radiotherapy for breast cancer remain elusive. To unravel the genetic basis for radiation-induced late skin toxicity, we carried out targeted next-generation sequencing of germline DNA samples from 48 breast cancer patients with extreme late skin toxicity phenotypes, consisting of 24 cases with grade 2–3 subcutaneous fibrosis and/or grade 2–3 telangiectasia (LENT-SOMA scales) and 24 controls with grade 0 fibrosis and grade 0 telangiectasia. In this exploratory study, a total of five single-nucleotide variants (SNVs) located in three genes (TP53, ERCC2, and LIG1) reached nominal levels of statistical significance (p < 0.05). In the replication study, which consisted of an additional 45 cases and 192 controls, none of the SNVs identified by targeted NGS achieved nominal replication. Nevertheless, TP53 rs1042522 (G > C, Pro72Arg) in the replication cohort had an effect (OR per C allele: 1.52, 95%CI: 0.82–2.83, p = 0.186) in the same direction as in the exploratory cohort (OR per C allele: 4.70, 95%CI: 1.51–14.6, p = 0.007) and was found be nominally associated to the risk of radiation-induced late skin toxicity in the overall combined cohort (OR per C allele: 1.79, 95%CI: 1.06–3.02, p = 0.028). These results raise the possibility of an association between TP53 rs1042522 and risk of radiation-induced late skin toxicity in breast cancer patients; however, large replication studies are warranted for conclusive evidence.

Factors Influencing the Severity of Acute Radiation-Induced Skin and Mucosal Toxicity in Head and Neck Cancer.

Background and purposeRadiotherapy is a crucial part of cancer therapy armamentarium, but it is associated with skin and mucosal toxicity in a substantial proportion of patients with head and neck cancer. Its extent, however, depends on several patient-related and treatment-related factors. In-depth knowledge of these is prudent for better patient management.AimThe aim of this study is to assess the factors influencing the severity of acute radiation-induced skin and mucosal toxicity in patients with head and neck cancer receiving external beam radiotherapy.Materials and methodsThis longitudinal observational study included all patients receiving curative external beam radiotherapy for head and neck cancer aged 18 years or above from January 2018 to December 2018. Patient-related and treatment-related characteristics including age, gender, type, staging and site of cancer, history of smoking and diabetes, surface area exposed, and concurrent chemotherapy were compared in patients experiencing severe and non-severe acute skin and mucosal toxicity using the Radiation Therapy Oncology Group (RTOG) scoring system.ResultsHigher age (p = 0.002), TNM stage IV (p = 0.023), and concurrent administration of chemotherapy (p = 0.002) were statistically associated with severe acute radiation-induced skin and mucosa toxicity, whereas gender, surface area irradiated, history of smoking, and diabetes did not show such an association.ConclusionOlder patients with TNM stage IV malignancy receiving concurrent chemotherapy are at a high risk of developing skin and mucosal toxicity that might interfere with the treatment protocol and warrant hospitalization, compromising their quality of life.

PO-1130 Radiation Induced Skin Toxicity after HypoFractionated Radiotherapy: A prospective analysis

PO-1130 Radiation Induced Skin Toxicity after HypoFractionated Radiotherapy: A prospective analysis

A Parallel, Observer Blind Study of the Skin Protection Properties of Silicone-Based Gels after Radiotherapy Exposure

Objective: Radiotherapy of cancers are usually accompanied by some form of radiation induced skin toxicity (radiation dermatitis) in most patients receiving this type of treatment. It can vary from very mild disease to extensive and severe dermatitis limiting further treatment. It is therefore obvious that preventative care will optimise the outcome of radiation of the tumour while the skin’s integrity is preserved leading to a better clinical outcome overall. Methods: In Vitro: In the study a newly developed silicone topical device (RT-Gel Sun Pharma South Africa), is compared to a similar product StrataXRT as well as to a negative control group of no gel. Gels were tested to observe the effect on the radiation dose provided. All gels were applied as a thin layer to the surface of the bolus within the Farmer Chamber. In Vivo: In this multicentre study a newly developed silicone topical device (RT-Gel® Sun Pharma South Africa), applied as a thin layer gel, is compared to a similar product StrataXRT as well as to standard of care in practice. The aim was to compare patients’ preferences of treatment modalities as well as establishing differences in clinical outcomes focussing on grades of skin toxicity after radiation therapy. Patients were recruited at radiation oncology sites after being prescribed radiation dosages with curative intent for mostly breast and head and neck cancers. Results: In Vitro: The uncertainties pertaining to the theoretical dose changes and radiation measurements indicates clearly the differences caused by the application of a silicone-based gel during radiotherapy is small enough to be regarded as negligible. In Vivo: The primary outcomes demonstrate the patient’s satisfaction with RT-Gel® i.e. a significant preference for RT-Gel compared to both StrataXRT® (p&lt; 0.02) and standard of care (p&lt; 0.001). The clinicians’ toxicity scores also favoured RT-Gel® over StrataXRT (p&lt; 0.04 ANOVA). Conclusion: It can thus be concluded that preventative treatment with RT-Gel® is at least as effective if not better than competitors, well tolerated and preferred by patients. . It furthermore indicates that dose is not affected by gel and that washing of treated area before next treatment is not required to “prevent build-up of gel”.

FLASH Proton Pencil Beam Scanning Irradiation Minimizes Radiation-Induced Leg Contracture and Skin Toxicity in Mice.

Simple SummaryDose and efficacy of radiation therapy are limited by the toxicity to normal tissue adjacent to the treated tumor region. Recently, ultra-high dose rate radiotherapy (FLASH radiotherapy) has shown beneficial reduction of normal tissue damage while preserving similar tumor efficacy with electron, photon and scattered proton beam irradiation in preclinical models. Proton therapy is increasingly delivered by pencil beam scanning (PBS) technology, and we therefore set out to test PBS FLASH radiotherapy on normal tissue toxicity and tumor control in vivo in mouse using a clinical proton delivery system. This validation of the FLASH normal tissue-sparing hypothesis with a clinical delivery system provides supporting data for PBS FLASH radiotherapy and its potential role in improving radiotherapy outcomes. Ultra-high dose rate radiation has been reported to produce a more favorable toxicity and tumor control profile compared to conventional dose rates that are used for patient treatment. So far, the so-called FLASH effect has been validated for electron, photon and scattered proton beam, but not yet for proton pencil beam scanning (PBS). Because PBS is the state-of-the-art delivery modality for proton therapy and constitutes a wide and growing installation base, we determined the benefit of FLASH PBS on skin and soft tissue toxicity. Using a pencil beam scanning nozzle and the plateau region of a 250 MeV proton beam, a uniform physical dose of 35 Gy (toxicity study) or 15 Gy (tumor control study) was delivered to the right hind leg of mice at various dose rates: Sham, Conventional (Conv, 1 Gy/s), Flash60 (57 Gy/s) and Flash115 (115 Gy/s). Acute radiation effects were quantified by measurements of plasma and skin levels of TGF-β1 and skin toxicity scoring. Delayed irradiation response was defined by hind leg contracture as a surrogate of irradiation-induced skin and soft tissue toxicity and by plasma levels of 13 different cytokines (CXCL1, CXCL10, Eotaxin, IL1-beta, IL-6, MCP-1, Mip1alpha, TNF-alpha, TNF-beta, VEGF, G-CSF, GM-CSF and TGF- β1). Plasma and skin levels of TGF-β1, skin toxicity and leg contracture were all significantly decreased in FLASH compared to Conv groups of mice. FLASH and Conv PBS had similar efficacy with regards to growth control of MOC1 and MOC2 head and neck cancer cells transplanted into syngeneic, immunocompetent mice. These results demonstrate consistent delivery of FLASH PBS radiation from 1 to 115 Gy/s in a clinical gantry. Radiation response following delivery of 35 Gy indicates potential benefits of FLASH versus conventional PBS that are related to skin and soft tissue toxicity.

Study of the various cutaneous adverse reactions to radiotherapy

&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Radiation-induced skin toxicity is a widely recorded toxicity of definitive radiation therapy with about half of patients experiencing grade 2 or higher skin reactions. Radiation-specific characteristics include total exposure, fractional dose, beam energy, field size, anatomic of radiation, and subsequent systemic therapy.&lt;strong&gt; &lt;/strong&gt;Aim of the study was to identify and grade the various cutaneous adverse reactions to radiotherapy.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;25 patients underwent radiation therapy for any type malignancies were included in the study.&lt;strong&gt; &lt;/strong&gt;Skin manifestations due to other systemic/ cutaneous diseases prior to radiotherapy. Detailed history was taken about disease course, cutaneous manifestations with emphasis on treatment (type of radiation, dosage and duration). General physical examination and dermatological examination were done.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In this study 60% of patients were male, the minimum dose of radiation was 30Gy in 13% patients, maximum dose of radiation was 70Gy in 33% patients, 88% of patients were in RTOG grade 2. Hyperpigmentation was the commonest findings 23 (92%), followed by dry desquamation 11 (44%), the next common was epilation 10 (40%).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Radiation toxicity, generally occurring during or shortly after treatment can range from mild (hyperpigmentation, erythema) to severe (moist desquamation).&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt; &lt;/strong&gt;&lt;/p&gt;