Clinically Significant Dermatitis During Adjuvant Radiotherapy for Invasive Breast Cancer.

BACKGROUND/AIM: Patients with breast cancer receiving adjuvant radiotherapy may experience grade ≥2 dermatitis. In the Interreg-project HeAT, a mobile application (app) reminding patients to perform skin care will be prospectively tested with the goal of decreasing clinically significant radiation dermatitis. This study aimed to identify the prevalence of grade ≥2 dermatitis and risk factors, required for designing the prospective trial. PATIENTS AND METHODS: In a retrospective study of 327 patients with breast cancer irradiated during 2022-2023, the prevalence of grade ≥2 dermatitis and 23 potential risk factors were investigated. RESULTS: The prevalence of grade ≥2 dermatitis was 31.2%. On multivariate analysis, it was significantly associated with chronic inflammatory disease (p=0.001), significant cardiovascular disease (p<0.001), smoking history >10 pack years (p<0.001), advanced T-stage (p=0.017), normo-fractionation (p<0.001), and radiation boost (p<0.001). CONCLUSION: The prevalence of grade ≥2 dermatitis and independent risk factors during adjuvant radiotherapy for invasive breast cancer were identified that contribute to improved patient care and the design of a prospective trial.

Incidence of radiodermatitis and factors associated with its severity in women with breast cancer: a cohort study.

BACKGROUND: One of the main adverse reactions of adjuvant radiotherapy for breast cancer is radiodermatitis. OBJECTIVE: To assess the incidence of radiodermatitis in women with breast cancer, identify factors associated with its severity and determine the time at which this event occurs. METHODS: Prospective cohort study in 113 women with breast cancer who were evaluated before radiotherapy and at every fifth session until the end of treatment. Logistic regression and Cox proportional regression model were used for the assessment of risk factors; P values < 0.05 were considered significant. RESULTS: The incidence rate of radiodermatitis was 98.2% and it was demonstrated that for each additional point of the Body Mass Index (BMI), the chance of occurrence of grades II to IV radiodermatitis increases by 14% (OR=1.14 [95% CI 1.04-1.26]; p=0.004) and statin use increases the risk of more severe skin lesions by four-fold (OR=4.27 [95% CI 1.11-16.42]; p=0.035). The exclusive use of hydrogel for skin hydration was an independent factor in delaying the onset of radiodermatitis (HR=0.55 [95% CI 0.36-0.82]; p=0.004). STUDY LIMITATIONS: The main limitation of this study was its external validity. The identified factors should be considered for services and populations similar to those in this study. CONCLUSIONS: There was a high incidence of radiodermatitis and its severity was related to higher BMI, statin use; there was a protective effect of hydrogel use.

Radiation Dermatitis and Pneumonitis in Patients Irradiated for Breast Cancer.

BACKGROUND/AIM: Adjuvant radiotherapy (RT) for breast cancer can be associated with acute dermatitis (ARD) and pneumonitis (RP). Prevalence and risk factors were characterized. PATIENTS AND METHODS: This study included 489 breast cancer patients receiving adjuvant RT with conventional fractionation (CF) ± sequential or simultaneous integrated boost, or hypo-fractionation ± sequential boost. RT-regimen and 15 characteristics were investigated for grade ≥2 ARD and RP. RESULTS: Prevalence of grade ≥2 ARD and RP was 25.3% and 2.5%, respectively. On univariate analyses, ARD was significantly associated with CF and radiation boost (p<0.0001), age ≤60 years (p=0.008), Ki-67 ≥15% (p=0.012), and systemic treatment (p=0.002). On multivariate analysis, RT-regimen (p<0.0001) and age (p=0.009) were associated with ARD. Chronic inflammatory disease was significantly associated with RP on univariate (p=0.007) and multivariate (p=0.016) analyses. CONCLUSION: Risk factors for grade ≥2 ARD and RP were determined that may help identify patients who require closer monitoring during and after RT.

Risk assessment, surveillance, and nonpharmaceutical prevention of acute radiation dermatitis: results of a multicentric survey among the German-speaking radiation oncology community.

PURPOSE: Radiation dermatitis (RD) represents one of the most frequent side effects in radiotherapy (RT). Despite technical progress, mild and moderate RD still affects major subsets of patients and identification and management of patients with a high risk of severe RD is essential. We sought to characterize surveillance and nonpharmaceutical preventive management of RD in German-speaking hospitals and private centers. METHODS: We conducted a survey on RD among German-speaking radiation oncologists inquiring for their evaluation of risk factors, assessment methods, and nonpharmaceutical preventive management of RD. RESULTS: A total of 244 health professionals from public and private institutions in Germany, Austria, and Switzerland participated in the survey. RT-dependent factors were deemed most relevant for RD onset followed by lifestyle factors, emphasizing the impact of treatment conceptualization and patient education. While a broad majority of 92.8% assess RD at least once during RT, 59.0% of participants report RD at least partially arbitrarily and 17.4% stated to classify RD severity solely arbitrarily. 83.7% of all participants were unaware of patient-reported outcomes (PROs). Consensus exists on some lifestyle recommendations like avoidance of sun exposure (98.7%), hot baths (95.1%), and mechanical irritation (91.8%) under RT, while deodorant use (63.4% not at all, 22.1% with restrictions) or application of skin lotion (15.1% disapproval) remain controversial and are not recommended by guidelines or evidence-based practices. CONCLUSION: Identification of patients at an increased risk of RD and subsequent implementation of adequate preventive measures remain relevant and challenging aspects of clinical routines. Consensus exists on several risk factors and nonpharmaceutical prevention recommendations, while RT-dependent risk factors, e.g., the fractionation scheme, or hygienic measures like deodorant use remain controversial. Surveillance is widely lacking methodology and objectivity. Intensifying outreach in the radiation oncology community is needed to improve practice patterns.

Radiation-induced skin changes after breast or chest wall irradiation in patients with breast cancer and skin of color: a systematic review.

INTRODUCTION: The purpose of this study is to systematically review data pertaining to breast cancer and radiation-induced skin reactions in patients with skin of color (SOC), as well as data pertaining to objective measurements of skin pigmentation in the assessment of radiation dermatitis (RD). METHODS AND MATERIALS: We conducted a systematic review utilizing MEDLINE electronic databases to identify published studies until August 2022. Key inclusion criteria included studies that described RD in breast cancer with data pertaining to skin of color and/or characterization of pigmentation changes after radiation. RESULTS: We identified 17 prospective cohort studies, 7 cross-sectional studies, 5 retrospective studies and 4 randomized controlled trials. Prospective cohort and retrospective series demonstrate worse RD in African American (AA) patients using subjective physician-graded scales. There is more limited data in patients representing other non-White racial subgroups with SOC. 2 studies utilize patient reported outcomes and 15 studies utilize objective methods to characterize pigmentation change after radiation. There are no prospective and randomized studies that objectively describe pigmentation changes with radiotherapy in SOC. CONCLUSIONS: AA patients appear to have worse RD outcomes, though this is not uniformly observed across all studies. There are no studies that describe objective measures of RD and include baseline skin pigmentation as a variable, limiting the ability to draw uniform conclusions on the rate and impact of RD in SOC. We highlight the importance of objectively characterizing SOC and pigmentation changes before, during and after radiotherapy to understand the incidence and severity of RD in SOC.

Incidence of radiodermatitis in breast cancer patients during hypofractionated radiotherapy.

OBJECTIVE: To analyze the incidence, dose of occurrence, grade, severity, and associated risk factors for the development of radiodermatitis, by area of the irradiated breast, in women with breast cancer, during hypofractionated radiotherapy. METHOD: Observational, prospective, and longitudinal study, according to the guidelines of the Strengthening the Reporting of Observational studies in Epidemiology, carried out between May 2019 and May 2021. RESULTS: A total of 104 women participated in the study, and 73.1% (95%CI: 64-82) developed signs of radiodermatitis during treatment. The majority (63.5%, 95%CI: 54-73) developed erythema in the axillary region with about 36.5 Grays. Women with large breasts and statin users are more likely to develop radiodermatitis. However, women with Phototype III skin color classification (light brown skin) are less likely to develop radiodermatitis, with skin color being a protective factor. CONCLUSION: The incidence of radiodermatitis in women with breast cancer during hypofractionated radiotherapy is significant. Therefore, the development of protocols for the management of this radiotoxicity is suggested, considering the cumulative dose and associated risk factors.

Radiation recall dermatitis induced by COVID-19 vaccination in breast cancer patients treated with postoperative radiation therapy.

BACKGROUND: and purpose: Radiation recall dermatitis is an adverse event predominantly due to systemic therapy administration after a previous radiation therapy course. Few case reports describe radiation recall dermatitis in breast cancer patients treated with postoperative radiation therapy following COVID-19 vaccination. In this study we investigated the incidence and severity of radiation recall dermatitis after COVID-19 vaccination in irradiated breast cancer patients. METHODS: Patients that received at least one COVID-19 vaccination dose during the year after the end of postoperative breast radiation therapy were included in this observational monocentric study. Local symptoms occurring inside the radiation field after vaccination were patient-reported and scored according to the PRO-CTCAE questionnaire. Descriptive data of radiation recall dermatitis incidence and severity, and potential risk factors were evaluated. RESULTS: A cohort of 361 patients with 756 administered COVID-19 vaccinations was analyzed. Breast symptoms were reported by 7.5% of patients, while radiation recall dermatitis was considered for 5.5%. The incidence of radiation recall dermatitis per single dose of vaccine was 2.6%, with a higher risk for the first dose compared to the second/third (4.4% vs 1%, p = 0.003), especially when administered within the first month after the end of irradiation (12.5% vs 2.2%, p = 0.0004). Local symptoms were generally self-limited and a few cases required anti-inflammatory drugs. CONCLUSIONS: Radiation recall dermatitis is an uncommon but not rare phenomenon in breast cancer patients that received COVID-19 vaccination within one year after breast irradiation. However, symptoms severity were generally low/mild and reversible. These findings can be useful for patient counseling.

Radiation recall dermatitis: A review of the literature.

PURPOSE/OBJECTIVES: Radiation recall dermatitis (RRD) is a skin reaction limited to an area of prior radiation triggered by the subsequent introduction of systemic therapy. To characterize RRD, we conducted a literature search, summarized RRD features, and compared the most common drug classes implicated in this phenomenon. MATERIALS/METHODS: PubMed, Embase, Scopus, Web of Science, and Cochrane DBSR databases were queried through July 1, 2019 using key words: radiation recall, RRD, and radiodermatitis (limited to humans and English language). Studies included case reports in which patients treated with radiotherapy were initiated on a new line of systemic therapy and subsequently developed a skin reaction in the irradiated area. RRD cases were organized by whether RRD occurred after a single drug or multiple drug administration. RESULTS: One-hundred fifteen studies representing 129 RRD cases (96 single-drug RRD, 33 multi-drug) were included. Sixty-three drugs were associated with RRD. Docetaxel (22) and gemcitabine (18) were the two drugs most commonly associated with RRD. Breast cancer (69 cases) was the most commonly associated tumor type. For single-drug RRD, the median radiotherapy dose was 45.0 Gy (range, 30.0-63.2 Gy). The median time from radiotherapy to drug exposure, time from drug exposure to RRD and time to significant improvement was 8 weeks (range, 2-132 weeks), 5 days (range, 2-56 days), and 14 days (range, 7-49 days), respectively. Variables significantly associated with grade ≥2 toxicity were docetaxel (P = 0.04) and non-antifolate antimetabolite (P = 0.05). The only variable significantly associated with grade ≥3 toxicity was capecitabine (P = 0.04). CONCLUSIONS: RRD is a complex toxicity that can occur after a wide range of radiotherapy doses and many different systemic agents. Most commonly, it presents in patients diagnosed with breast cancer and after administration of a taxane or antimetabolite medication. RRD treatment generally consists of corticosteroids with consideration of antibiotics if superinfection is suspected. Drug re-challenge may be considered after RRD if the initial reaction was of mild intensity.

[Prognostic factors of acute radiodermatitis in breast cancer after adjuvant radiotherapy treated with RT3D or IMRT]. / Étude des facteurs pronostiques de radiodermite aiguë dans le cancer du sein traité par irradiation conformationnelle adjuvante avec ou sans modulation d'intensité.

PURPOSE: Real life study of prognostic factors of acute radiodermatitis in a monocentric cohort of 200 patients with breast cancer treated with RT3D or IMRT for adjuvant radiotherapy. PATIENTS AND METHODS: This study comprises 200 patients with breast cancer treated with adjuvant radiotherapy, included consecutively. For each patient, their clinical and tumoral characteristics and the irradiation schedule was retrospectively collected. The severity of acute radiodermatitis was also collected, during the treatment and 6weeks after the end of irradiation. The objective was to identify risk factors for acute radiodermatitis grade≥2. RESULTS: The univariate analysis found that a more important BMI (p<0.001), a more important volume of PTV (p<0.001) a normofractionated schedule (p=0.002) were statistically associated to a greater risk of occurrence of grade≥2 acute radiodermatitis. The multivariate analysis found BMI>30 (OR=9.31, p=0.04), light phototype (OR=0.04, p=0.02) and histology other than invasive breast carcinomas (OR=0.07, p=0.04) to be statistically associated to the occurrence of grade≥2 acute radiodermatitis. CONCLUSION: In this monocentric retrospective study, with a prospective collection of the severity of acute radiodermatitis, no grade 3 radiodermatitis has been observed and the frequency of occurrence of grade 2 radiodermatitis was lower than previously published. In contrast to previously published results, IMRT was not associated to a lower risk of grade≥2 acute radiodermatitis. Multivariate analysis found BMI, phototype, and histology to be risk factors of grade≥2 acute radiodermatitis.

Incidence of acute radiodermatitis in women with breast cancer undergoing hypofractionated radiotherapy.

OBJECTIVE: To estimate the incidence and degree of acute radiodermatitis at the end and after the end of treatment in women with breast cancer undergoing hypofractionated radiotherapy. METHODS: Observational, prospective, and longitudinal study, conducted between March 2019 and January 2020, in a radiotherapy outpatient clinic. RESULTS: Thirty-two women participated in the study, among whom, in the last session of hypofractionated radiotherapy, 15 (46.9%) had radiodermatitis, erythema in 13 (40.6%), and wet peeling in 2 (6.3%). In the post-treatment evaluation, 27 (84.4%) had radiodermatitis, erythema in 17 (53.1%), dry peeling in 8 (25%), and wet peeling in 2 (6.3%). CONCLUSION: The general incidence of radiodermatitis after hypofractionated radiotherapy in women with breast cancer was 37.5%, erythema, 12.5%, and dry peeling, 25%. The development of care protocols for the management of radiodermatitis after treatment is of paramount importance.

Prognostic Nutritional Index Predicts Toxicity in Head and Neck Cancer Patients Treated with Definitive Radiotherapy in Association with Chemotherapy.

BACKGROUND: The Prognostic Nutritional Index (PNI) is a parameter of nutritional and inflammation status related to toxicity in cancer treatment. Since data for head and neck cancer are scanty, this study aims to investigate the association between PNI and acute and late toxicity for this malignancy. METHODS: A retrospective cohort of 179 head and neck cancer patients treated with definitive radiotherapy with induction/concurrent chemotherapy was followed-up (median follow-up: 38 months) for toxicity and vital status between 2010 and 2017. PNI was calculated according to Onodera formula and low/high PNI levels were defined according to median value. Odds ratio (OR) for acute toxicity were calculated through logistic regression model; hazard ratios (HR) for late toxicity and survival were calculated through the Cox proportional hazards model. RESULTS: median PNI was 50.0 (interquartile range: 45.5-53.5). Low PNI was associated with higher risk of weight loss > 10% during treatment (OR = 4.84, 95% CI: 1.73-13.53 for PNI < 50 versus PNI ≥ 50), which was in turn significantly associated with worse overall survival, and higher risk of late mucositis (HR = 1.84; 95% CI:1.09-3.12). PNI predicts acute weight loss >10% and late mucositis. CONCLUSIONS: PNI could help clinicians to identify patients undergoing radiotherapy who are at high risk of acute and late toxicity.

Acute radiodermatitis in cancer patients: incidence and severity estimates.

OBJECTIVE: To estimate the incidence and distribution of the degree of radiodermatitis in cancer patients submitted to radiotherapy in the regions of head and neck, breast, and pelvis. METHOD: Prospective, longitudinal, quantitative study conducted from March 15, 2016 to May 4, 2017 with patients observed for five weeks of treatment. The primary outcome was the proportion of grade 1 or higher radiodermatitis each week. The degree of radiodermatitis and mean time of occurrence for each patient were secondary outcomes. RESULTS: This study included 112 patients. The incidence of radiodermatitis was 100% among those whose head and neck region was irradiated, followed by 98% for breast and 48% for the pelvic region. The degree of radiodermatitis varied with the irradiated site; the worst degrees were found in the head and neck region, followed by the breast. In the three groups, the mean time of the first occurrence of radiodermatitis was approximately eleven days. CONCLUSION: The incidence of radiodermatitis in the studied groups was high, which reinforces the need to perform the same evaluation nationwide. This would support creating and standardizing protocols and recommendations for a proper management of radiodermatitis, specially concerning its prevention.

Palliative radiation therapy for symptomatic advance breast cancer.

In this study, we evaluated the effectiveness of palliative breast radiation therapy (RT), with single fraction RT compared with fractionated RT. Our study showed that both RT fractionation schemas provide palliation. Single fraction RT allowed for treatment with minimal interference with systemic therapy, whereas fractionated RT provided a more durable palliative response. Due to equivalent palliative response, at our institution we have increasingly been providing single fraction RT palliation during the COVID-19 pandemic.

A prospective feasibility study of a 1-mm bolus for postmastectomy radiotherapy.

BACKGROUND: The optimal chest wall bolus regimen for postmastectomy radiotherapy (PMRT) remains unknown. We aimed to prospectively evaluate the use of a 1-mm-thick daily tissue-equivalent bolus in patients who received PMRT using thermoluminescent dosimeters (TLDs) and skin toxicity assessment. METHODS: Patients with a 1-mm-thick daily bolus during PMRT were prospectively enrolled at The Juntendo University Hospital. The surface dose was measured in vivo under the 1-mm-thick bolus on the chest wall. We assessed the acute skin toxicity weekly during PMRT, and 1, 2, 4, and 12 weeks after the completion of PMRT. RESULTS: A total of 19 patients aged 32-79 years old received PMRT from July 2019 to January 2020. All patients completed the protocol treatment without interruptions, and the median follow-up was 32 weeks. In vivo dosimetry analysis revealed surface doses between 77 and 113% of the prescribed dose, with a mean of 92% of the prescribed radiation dose, and a standard deviation of 7% being delivered. Grade 2 dermatitis was found in 10 patients (53%), and Grade 3 dermatitis was found in one patient (5%). All cases of Grade 2 and 3 dermatitis were improved 4 weeks after PMRT. There were no cases of Grade 4 dermatitis and no chest wall recurrences during the treatment or follow-up period. CONCLUSIONS: Results confirmed the feasibility of using a 1-mm-thick daily bolus for PMRT, exhibiting an appropriate dose buildup and acceptable skin toxicity without treatment interruptions. TRIAL REGISTRATION: The University Hospital Medical Information Network Clinical Trials Registry, UMIN000035773 . Registered 1 July 2019.

Preditores e qualidade de vida em pacientes com radiodermatite: estudo longitudinal / Predictores y calidad de vida en pacientes con radiodermatitis: estudio longitudinal / Predictors and quality of life in patients with radiodermatitis: a longitudinal study

Resumo Objetivo: Analisar os preditores sociodemográficos, clínicos e terapêuticos e a qualidade de vida em pacientes com radiodermatite. Métodos: Trata-se de um estudo longitudinal, realizado com 196 pessoas que desenvolveram reações cutâneas como evento adverso ao tratamento radioterápico. Foi utilizado um formulário para caracterização e avaliação clínica e o instrumento European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 para mensuração da qualidade de vida em duas etapas. A análise dos dados foi constituída pelos testes Wilcoxon, Mann-Whitney e Kruskal-Wallis , considerando diferença estatisticamente significativa para p < 0,05. Resultados: A comparação entre os escores de qualidade de vida mostrou que a radiodermatite contribuiu para piora do estado global de saúde e da qualidade de vida, deterioração da capacidade funcional, dificuldade financeira e intensificação de reações emocionais e de sintomas físicos como ansiedade, depressão, dor, fadiga, insônia e falta de apetite. Fatores como sexo, renda, escolaridade, quimioterapia concomitante, localização anatômica da lesão e grau de destruição tecidual foram determinantes para o maior comprometimento dos escores globais. Diante disso, surge a necessidade de intervenções de enfermagem que favoreçam a identificação de preditores e que otimizem o cuidado a partir de diretrizes e recomendações clínicas. Conclusão: A radiodermatite influenciou negativamente a qualidade de vida dos pacientes, tendo alto impacto associado ao maior grau de destruição tecidual e como principais preditores destacaram-se os aspectos clínicos e terapêuticos. Estudos dessa natureza são imprescindíveis para formulação de políticas públicas efetivas, integradas, sustentáveis e baseadas em evidências voltadas para prevenção, controle e tratamento da lesão.

Resumen Objetivo: Analizar los predictores sociodemográficos, clínicos y terapéuticos y la calidad de vida en pacientes con radiodermatitis. Métodos: Se trata de un estudio longitudinal, realizado con 196 personas que presentaron reacciones cutáneas como evento adverso al tratamiento radioterápico. Se utilizó un formulario para la caracterización y evaluación clínica y el instrumento European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 para la medición de calidad de vida en dos etapas. El análisis de los datos se realizó a través de las pruebas Wilcoxon, Mann-Whitney y Kruskal-Wallis , considerando una diferencia estadísticamente significativa de p < 0,05. Resultados: La comparación entre las puntuaciones de calidad de vida demostró que la radiodermatitis contribuyó con el empeoramiento del estado global de salud y de la calidad de vida, el deterioro de la capacidad funcional, la dificultad financiera y la intensificación de reacciones emocionales y de síntomas físicos como ansiedad, depresión, dolor, fatiga, insomnio y falta de apetito. Factores como sexo, ingresos, escolaridad, quimioterapia simultánea, ubicación anatómica de la lesión y nivel de destrucción tisular fueron determinantes para un mayor comprometimiento de la puntuación global. Ante esto, surge la necesidad de intervenciones de enfermería que favorezcan la identificación de predictores y que optimicen el cuidado a partir de directrices y recomendaciones clínicas. Conclusión: La radiodermatitis influyó negativamente en la calidad de vida de los pacientes, con un alto impacto relacionado con un mayor nivel de destrucción tisular, y como principales predictores se destacaron los aspectos clínicos y terapéuticos. Estudios de esta naturaleza son imprescindibles para la formulación de políticas públicas efectivas, integradas, sustentables y basadas en evidencias orientadas hacia la prevención, control y tratamiento de la lesión.

Abstract Objective: To analyze sociodemographic, clinical and therapeutic predictors and quality of life in patients with radiodermatitis. Methods: This longitudinal study was conducted with 196 participants who developed skin reactions as an adverse event to radiotherapy treatment. A form was used for clinical characterization and evaluation, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 instrument was used for measuring the quality of life in two stages. Data analysis consisted of the Wilcoxon, Mann-Whitney and Kruskal-Wallis tests, considering a statistically significant difference for p<0.05. Results: The comparison between scores of the quality of life showed that radiodermatitis contributed to the worsening of overall health status and quality of life, deterioration of functional capacity, financial difficulty and intensification of emotional reactions and physical symptoms such as anxiety, depression, pain, fatigue, insomnia and appetite loss. Factors such as sex, income, educational level, concomitant chemotherapy, anatomical location of the injury and degre of tissue destruction were determinant for the greater impairment of global scores. Thus, the need for nursing interventions that favor the identification of predictors and care optimization based on clinical guidelines and recommendations. Conclusion: Radiodermatitis negatively influenced the quality of life of patients, had a high impact associated with a greater degree of tissue destruction and the main predictors were clinical and therapeutic aspects. Studies of this nature are essential for the formulation of effective, integrated, sustainable and evidence-based public policies aimed at preventing, controlling and treating the injury.

Comparison of two radiation boost schedules in postlumpectomy patients with breast cancer.

BACKGROUND: We have been practicing hypofractionation, 40 Gy in 16 fractions over 3 weeks for whole breast irradiation (WBI) for the past five decades with or without boost at our center. In this study, we compared two boost schedules of 10 Gy/5#/1 week with 16 Gy/8#/1.5 weeks in postlumpectomy patients with breast cancer after WBI. MATERIALS AND METHODS: From June 2012 to June 2016, the study included 87 breast cancer patients postbreast conservation surgery. The institutional ethics committee approved the study, which was registered with ClinicalTrials.gov (ClinicalTrials.gov identifier no. CT02142907). All patients were treated with WBI of 40 Gy/16#/3 weeks. WBI was followed by tumor bed boost of 10 Gy/5#/1 week in 44 patients and 16 Gy/8#/1.5 weeks in 43 patients, either with electron beam therapy or 3D CRT with photons. The primary endpoint of the study was the comparison of local control between two schedules. Secondary endpoints were acute and late radiation toxicities, cosmetic score analysis, disease-free survival (DFS), and overall survival (OS). The assessment of acute and late skin toxicity was made as per RTOG scores and LENT-SOMA scale. The cosmetic assessment was made with Harvard/NSABP/RTOG Breast Cosmesis Grading Scale. RESULTS: Median follow-up was 55 months (range 18-78 months). Local recurrence was seen in 1 (2.3%) patient in the 16 Gy boost only. Acute Grade 2 skin toxicity was 33% in 16 Gy boost arm compared to 23% in 10 Gy boost arm. Late skin toxicities were also high in patients with 16 Gy boost. Grade ≥2 induration was seen in 4.5% and 14% of patients with 10 Gy and 16 Gy boost, respectively. None of the patients with 10 Gy boost had Grade 2 edema as compared to 5% with 16 Gy. Pigmentation was observed in 9% and 23% patients with 10 Gy and 16 Gy boost, respectively. Grade 1 fibrosis was 2% versus 12% in patients with 10 Gy and 16 Gy boost, respectively. The cosmetic score was good/excellent in 91% and 84% of patients with 10 Gy and 16 Gy boost, respectively. Distant metastasis occurred in 2 (4%) and 3 (7%) patients in 10 Gy and 16 Gy boost, respectively. DFS and OS at 5 years were comparable between the two boost schedules. CONCLUSION: Local control was comparable with 10 Gy and 16 Gy boost. Acute and late skin toxicities were higher with 16 Gy boost dose. The cosmetic score was better with 10 Gy boost. DFS and OS was comparable with the two boost schedules. Hence, a boost of 10 Gy/5# after WBI may be adequate in patients with breast cancer.

A reliable skin toxicity predictor in permanent breast seed implant brachytherapy.

PURPOSE: To establish skin dose-outcome relationships using a reliable metric in permanent breast seed implant (PBSI). METHODS: Sixty-seven consecutive patients who underwent PBSI at our institution were included. Skin doses were calculated using two skin dose indices: maximum point dose to the skin surface, Dmax, and D0.2cc for a 2-mm internal skin rind (a surrogate to the dose to 1 cm2 area of skin) from CT-based postoperative treatment plans. Toxicity data were extracted from patients' charts and photographs. The associations between skin dose and skin toxicity were investigated using the analysis of variance, and the predictive performance of skin dose measures was evaluated using receiver operating characteristic curves. RESULTS: For acute reactions, 49.3% of patients had Grade 1, 4.5% Grade 2, and 1.5% Grade 3 toxicity. For telangiectasia at 3 years, very minor and minimally apparent telangiectasia was observed in 25% of patients. Moderate but asymptomatic telangiectasia was observed in 9.1% of cases. Both metrics were significantly associated with the occurrence of acute toxicity and telangiectasia at 3 years (p < 0.01). The predictive values for Dmax and D0.2cc were 0.779 and 0.763, respectively, (p < 0.0001) for acute skin toxicity and 0.786 and 0.810 for telangiectasia (p < 0.0002). Extreme dose outliers (up to 878 Gy) and a high variability were observed for Dmax but not for D0.2cc, illustrating the superior reliability of D0.2cc. CONCLUSION: D0.2cc, as an alternate skin dose measure to Dmax, is a robust metric for measuring skin dose that is simple to calculate, yet is clinically relevant and not prone to inaccuracies inherent to point dose measurement.

Hypofractionated Whole Breast Irradiation and Simultaneous Integrated Boost in Large-breasted Patients: Long-term Toxicity and Cosmesis.

INTRODUCTION: The purpose of this study was to evaluate the impact of breast size on long-term toxicity and cosmesis in patients with breast cancer treated with hypofractionated simultaneous integrated boost (SIB) using volumetric modulated arc therapy (VMAT). PATIENTS AND METHODS: Patients with early stage breast cancer were treated with 3-week hypofractionated SIB-VMAT to the whole breast (40.5 Gy) and tumor bed (48 Gy). Two cohorts were identified: small/medium- (< 1000 cm3) and large- (> 1000 cm3) breasted patients. Acute and late (at 2 and 5 years) skin toxicity and cosmetic data were analyzed. Univariate and multivariate analysis evaluated associations between toxicity and dosimetric/anatomical variables. RESULTS: From August 2010 to March 2017, a total of 1160 patients were treated; 831 had at least 2 years of follow-up and were analyzed. Treated skin area (TSA) receiving at least 20 Gy > 400 cm2 and V105% of Boost > 5 cm3 were significant predictors for acute skin toxicity. Multivariate analysis at 2 years was significant for boost volume > 70 cm3, TSA > 400 cm2, and breast size > 1500 cm3. At 5 year analysis (352 patients), none of the analyzed variables was significant. For cosmetic outcome, only the breast size (> 1000 cm3) and the boost size > 70 cm3 at 2 and 5 years, respectively, confirmed significance. CONCLUSIONS: The TSA > 400 cm2 resulted as a significant predictor of both acute and late skin toxicity at 2 years; however, at 5 years, no breast size or dosimetric parameter suggested indications for increased toxicity. A worse cosmetic outcome was recorded at the 2-year follow up for large breasts, but was not confirmed at the 5-year follow-up. These long-term data suggest that hypofractionated SIB-VMAT is a viable modality also in large-breasted patients.

VITAL phase 2 study: Upfront 5-fluorouracil, mitomycin-C, panitumumab and radiotherapy treatment in nonmetastatic squamous cell carcinomas of the anal canal (GEMCAD 09-02).

AIM: VITAL, a phase II single-arm study, aimed to evaluate efficacy and safety of panitumumab addition to 5-fluorouracil (5-FU), mitomycin-C (MMC) and radiotherapy (RT) in patients with localized squamous cell carcinoma of the anal canal (SCCAC). METHODS: Adult, treatment-naïve SCCAC patients (Stage T2-T4, any N, M0) and ECOG-PS ≤2, received panitumumab (6 mg/kg, day 1 and Q2W; 8 weeks), 5-FU (1000 mg/m2 /d, days 1-4 and 29-32), MMC (10 mg/m2 , days 1 and 29) and RT 45 Gy (1.8 Gy/fraction) to the primary tumor and mesorectal, iliac and inguinal lymph nodes, plus 10-15 Gy boost dose to the primary tumor and affected lymph nodes. The primary objective was disease free survival rate (DFS) at 3-years (expected 3-year DFS rate: 73.7 ± 12%). RESULTS: Fifty-eight patients (31 women; median age: 59 years; ECOG-PS 0-1:98%; TNM II [29%] (T2 or T3/N0/M0)/IIIA (T1-T3/N1/M0 or T4/N0/M0) [21%]/IIIB (T4/N1/M0 or any T/N2 or N3/M0) [47%]/nonevaluable [4%]) were included. The median follow-up was 45 months. The 3-year DFS rate was 61.1% (95% CI: 47.1, 72.4). The 3-year overall survival rate was 78.4% (95% CI: 65.1, 87.1). Eighteen patients (31.0%) required a colostomy within 2 years posttreatment. Grade 3-4 toxicities were experienced by 53 (91%) patients. Most common grade 3-4 treatment-related events were radiation skin injury (40%) and neutropenia (24%). No toxic deaths occurred. Improved efficacy in colostomy-free survival and complete response rate was observed in human papilloma virus positive patients. CONCLUSIONS: Panitumumab addition to MMC-5FU regimen in SCCAC patients increases toxicity and does not improve patients' outcomes. RT plus MMC-5FU remains the standard of care for localized SCCAC patients.