Acute Radiation Skin Toxicity Research Articles

Experiences when irradiating grafts and flaps for skin cancer

"Resection of skin cancer with graft or flap repair may be referred for local postoperative radiotherapy (PORT) to ensure local control." PORT needs to be delivered in a certain time frame after surgery, but this may impact on graft and flap survival. The purpose of this article is to pass on some experience our multidisciplinary team has acquired in order to assist in the management of these cases. Specifically, pertinent issues in patient assessment (history and examination), indications for PORT, the differences between a graft and a flap, and technical considerations in the prescription of radiotherapy to these are covered, accompanied by illustrative cases with appropriate photographs and diagrams. The principal findings are that a conservative approach may need to be taken to ensure graft and flap survival, with PORT reserved for a role in salvage. Other interesting cases cover the lack of acute radiation side effects in flaps; the tendency of acute radiation skin toxicity to move with gravity, and transplanted skin may have a different radiation sensitivity to that of its new environment. We hope that this article will be of use for the multidisciplinary skin oncology team. Further research is needed to validate and confirm our findings.

The Intensity Modulated Radiotherapy vs . the 3D-Conformal Radiotherapy Regarding Acute Radiation Skin Toxicity and TreatmentRelated Lymphopenia in Early-Stage Breast Cancer Patients

Adjuvant radiotherapy is an integral part of breast cancer treatment, and there was a great evolution of radiotherapy techniques over the past few years. Intensity-modulated radiation therapy (IMRT) was developed in the 1990s as a modern technique aiming to spare normal tissues from toxic effects of radiotherapy. This study aimed at comparing the IMRT technique to the 3D-coformal radiotherapy technique (3D-CRT) in early breast cancer patients regarding the occurrence of acute skin toxicities and treatment-related lymphopenia (TRL). It is a prospective study conducted on 100 eligible patients who were divided equally between two groups; the first, are patients received adjuvant radiotherapy using IMRT technique and the second group were those who received 3D-CRT. Results showed that sever acute skin toxicity or moist desquamation in IMRT group was 6% vs. 18% in 3DCRT group (p<0.05). And, the sever TRL with IMRT technique was 9% compared 21% among those of the 3D-CRT group (p<0.05). The IMRT technique resulted in statistically significant lower incidence of sever acute skin toxicities as well as less sever TRL when compared with 3D-CRT technique.

Akutni radiodermatitis tokom zračne terapije

Acute radiation skin toxicity is the most common of all radiation toxicities during radiotherapy. More than 90% of the patients receiving radiotherapy have some form of radiodermatitis. There are many risk factors for radiodermatitis. The most important symptom is pain. Modern treatment technics, such as intensity modulated radiotherapy (IMRT) are giving for decreased severity and incidence of radiodermatitis. In treatment of acute skin radiation toxicity are necessary pain management and adequate skin care.

Fraction size in radiation therapy for breast conservation in early breast cancer.

Shortening the duration of radiation therapy would benefit women with early breast cancer treated with breast conserving surgery. It may also improve access to radiation therapy by improving efficiency in radiation oncology departments globally. This can only happen if the shorter treatment is as effective and safe as conventional radiation therapy. This is an update of a Cochrane Review first published in 2008 and updated in 2009. To assess the effect of altered radiation fraction size for women with early breast cancer who have had breast conserving surgery. We searched the Cochrane Breast Cancer Specialised Register (23 May 2015), CENTRAL (The Cochrane Library 2015, Issue 4), MEDLINE (Jan 1996 to May 2015), EMBASE (Jan 1980 to May 2015), the WHO International Clinical Trials Registry Platform (ICTRP) search portal (June 2010 to May 2015) and ClinicalTrials.gov (16 April 2015), reference lists of articles and relevant conference proceedings. No language or publication constraints were applied. Randomised controlled trials of altered fraction size versus conventional fractionation for radiation therapy in women with early breast cancer who had undergone breast conserving surgery. Two authors performed data extraction independently, with disagreements resolved by discussion. We sought missing data from trial authors. We studied 8228 women in nine studies. Eight out of nine studies were at low or unclear risk of bias. Altered fraction size (delivering radiation therapy in larger amounts each day but over fewer days than with conventional fractionation) did not have a clinically meaningful effect on: local recurrence-free survival (Hazard Ratio (HR) 0.94, 95% CI 0.77 to 1.15, 7095 women, four studies, high-quality evidence), cosmetic outcome (Risk ratio (RR) 0.90, 95% CI 0.81 to 1.01, 2103 women, four studies, high-quality evidence) or overall survival (HR 0.91, 95% CI 0.80 to 1.03, 5685 women, three studies, high-quality evidence). Acute radiation skin toxicity (RR 0.32, 95% CI 0.22 to 0.45, 357 women, two studies) was reduced with altered fraction size. Late radiation subcutaneous toxicity did not differ with altered fraction size (RR 0.93, 95% CI 0.83 to 1.05, 5130 women, four studies, high-quality evidence). Breast cancer-specific survival (HR 0.91, 95% CI 0.78 to 1.06, 5685 women, three studies, high quality evidence) and relapse-free survival (HR 0.93, 95% CI 0.82 to 1.05, 5685 women, three studies, moderate-quality evidence) did not differ with altered fraction size. We found no data for mastectomy rate. Altered fraction size was associated with less patient-reported (P < 0.001) and physician-reported (P = 0.009) fatigue at six months (287 women, one study). We found no difference in the issue of altered fractionation for patient-reported outcomes of: physical well-being (P = 0.46), functional well-being (P = 0.38), emotional well-being (P = 0.58), social well-being (P = 0.32), breast cancer concerns (P = 0.94; 287 women, one study). We found no data with respect to costs. We found that using altered fraction size regimens (greater than 2 Gy per fraction) does not have a clinically meaningful effect on local recurrence, is associated with decreased acute toxicity and does not seem to affect breast appearance, late toxicity or patient-reported quality-of-life measures for selected women treated with breast conserving therapy. These are mostly women with node negative tumours smaller than 3 cm and negative pathological margins.

Polymorphic Variants in Oxidative Stress Genes and Acute Toxicity in Breast Cancer Patients Receiving Radiotherapy.

PurposeReactive oxygen species (ROS) are generated as an indirect product of radiation therapy (RT). Genetic variation in genes related to ROS metabolism may influence the level of RT-induced adverse effects. We evaluated the potential association of single nucleotide polymorphism (SNP)–related response to radiotherapy injury in breast cancer patients undergoing RT.Materials and MethodsEighty patients receiving conventional RT were included. Acute effects were evaluated according to the Radiation Therapy Oncology Group (RTOG) scores. DNA was extracted from blood and buccal swab samples. SNPs were genotyped for GSTP1, GSTA1, SOD2, and NOS3 genes by polymerase chain reaction–based restriction fragment length polymorphism. Univariate analysis (odds ratios [ORs] and 95% confidence interval [CI]) and principal component analysis were used for correlation of SNPs and factors related to risk of developing ≥ grade 2 acute effects.ResultsSixty-five patients (81.2%) showed side effects, 32 (40%) presented moderate to severe acute skin toxicity, and 33 (41.2%) manifested minimal acute skin reactions by the end of treatment. In both univariate and multivariate analyses, nominally significant associations were found among body mass index (OR, 3.14; 95% CI, 8.5338 to 1.1274; p=0.022), breast size (OR, 5.11; 95% CI, 17.04 to 1.54; p=0.004), and grade ≥ 2 acute radiation skin toxicity. A significant association was also observed between NOS3 G894T polymorphism (OR, 9.8; 95% CI, 211.6 to 0.45; p=0.041) and grade ≥ 2 acute radiation skin toxicity in patients with neo-adjuvant chemotherapy treatment.ConclusionThe analysis of the factors involved in individual radiosensitivity contributed to the understanding of the mechanisms underlying this trait.

Abstract P1-15-19: Effects of statin use on skin toxicity during breast radiation therapy

Abstract Background: Recent San Antonio Breast Cancer Symposium abstracts have suggested that statin use confers a significant benefit in breast cancer risk reduction and specifically in the subset of inflammatory breast cancer. Additional studies evaluating the combination of statin use with various breast cancer treatments are currently on-going. The primary objective of this study was to determine the effects of statin use on acute skin toxicity during breast radiation therapy (RT). Methods: We performed a retrospective chart review of 325 patients diagnosed with breast cancer who underwent RT between 2004 and 2012. Of these, 227 patients were considered evaluable. Patients were excluded if the course of RT was fewer than 16 treatments. Patients were also excluded if follow-up at the end of RT was not obtainable. Of the evaluable patients, 46 were on statins at time of RT, while 181 were not. Patients were evaluated at two time points - midway through RT and at completion of RT. Skin reactions were measured using the RTOG grading system for acute radiation morbidity. Grade 1 reactions were erythema and slight skin atrophy. Grade 2 indicated follicular, faint or dull erythema/ epilation/dry desquamation/ decreased sweating. Grade 3 was tender or bright erythema, patchy moist desquamation/moderate edema. Lastly, Grade 4 was ulceration, hemorrhage, necrosis. Results: Our results showed a statistically significant increase in acute radiation skin toxicity in patients on statins at the time of radiation therapy. By the midway point of RT, 67% of the statin group had developed Grade 1-3 skin toxicity vs. only 42% of the control group. Odds ratio midway through RT was 2.75. By the completion of RT, 94% of the statin group compared with 67% of the control group had Grade 1-3 skin toxicity (p=0.005). Odds Ratio at completion of RT was 7.29. The statin group also progressed to more advanced stages of toxicity more rapidly than our control group. Grade 1 skin reactions were seen in 62% of our statin group vs. 41% of our control group midway through treatment (p=0.044). Grade 2-3 reactions were seen in almost 5% of patients in the statin group vs. 1% in the non-statin group midway through treatment. At the end of treatment, 48% of patients on statins had developed Grade 2-3 reactions when compared with 29% in the non-statin group (p=0.0199). These results still remained significant when controlled for chemotherapy use. Conclusion: Our study revealed that patients on statins developed acute skin toxicity at higher rates than our control group. These results were statistically significant at both the midway point as well as at the completion of RT. Study limitations include the small sample size and the retrospective nature of the study. Our data also raises the question of what effect statins may have on local recurrence rates as well as the potential effects of radiosensitization in various breast cancer cell lines. These results are hypothesis-generating and require larger retrospective analyses or prospective trials to verify this effect. Citation Format: Scott M Lieberman, Elizabeth Stone, Christopher Chen, Marlow Hernandez, Leah Roberts. Effects of statin use on skin toxicity during breast radiation therapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-19.

Common variants of eNOS and XRCC1 genes may predict acute skin toxicity in breast cancer patients receiving radiotherapy after breast conserving surgery

PurposeTo evaluate the impact of functional polymorphisms in genes related to DNA repair mechanisms (XRCC1, TP53, MSH2, MSH3, XPD), oxidative stress response (GSTP1, GSTA1, eNOS, SOD2) and fibroblast proliferation (TGFβ1) on the risk of acute skin toxicity in breast cancer patients receiving radiotherapy. Material and methodsSkin toxicity was scored according to the Radiation Therapy Oncology Group criteria in 286 breast cancer patients who received radiotherapy after breast conserving surgery. Genotyping was conducted by PCR-RFLP analysis and real-time PCR allelic discrimination assay on genomic DNA extracted from peripheral blood. ResultsIn the multivariate analysis, nominally significant associations, before multiple testing corrections, were found between XRCC1 T-77C (T carriers vs. CC, OR: 2.240, 95% CI: 1.015–4.941, P=0.046), eNOS G894T polymorphisms (TT vs. G carriers, OR: 2.473, 95% CI: 1.220–5.012, P=0.012), breast diameter (OR: 1.138, 95% CI: 1.001–1.293, P=0.048), boost dose-fractionation (3Gy vs. no boost, OR: 4.902, 95% CI: 1.458–16.483, P=0.010) and ⩾grade 2 acute radiation skin toxicity in breast cancer patients. ConclusionsAs our exploratory study suggests that XRCC1 T-77C and eNOS G874T may confer an increased risk of acute skin reactions to radiotherapy in breast cancer patients, further confirmatory studies are warranted to determine the clinical significance.

Wound complications following pre-operative radiotherapy for soft tissue sarcoma

Aims: We analysed wound complications in 43 patients with soft tissue sarcoma who were treated with combined pre-operative radiotherapy and surgery. Methods: All patients received the same protocol of pre-operative radiotherapy at our institution. Results: Thirty-six (84%) patients developed acute skin toxicity following radiotherapy. After wide local excision, 15 patients required primary soft tissue reconstruction with vascularized muscle transfer and four patients underwent free skin flap to enable wound closure as part of their primary surgery. Nineteen patients (44%) developed post-operative wound complications including 10 (23%) patients who required an additional surgical procedure. Four (27%) patients developed flap necrosis in a group of 15 who underwent primary vascularized soft tissue transfer. All required a second vascularized muscular flap. One elderly patient, who had grade 3 acute radiation skin toxicity, had an arterial graft and total hip arthroplasty for a femoral artery aneurysm and an avascular necrosis of the hip, respectively. In our series, age (≥40 years) was the only impact factor influencing wound complication after surgery following radiotherapy (P=0.06). Conclusions: Site of tumour, radiation field size, surgical resection volume, grade of acute radiation toxicity, co-morbidity, and smoking were not demonstrated to have predictive value in wound complication following pre-operative radiotherapy. Although previous papers suggested that vascularized soft tissue transfer could be useful reducing wound morbidity, our results could not confirm this.