Spectrophotometer and ultrasound evaluation of late toxicity following breast-cancer radiotherapy.
ABSTRACT: Radiation-induced normal-tissue toxicities are common, complex, and distressing side effects that affect 90% of patients receiving breast-cancer radiotherapy and 40% of patients post radiotherapy. In this study, the authors investigated the use of spectrophotometry and ultrasound to quantitatively measure radiation-induced skin discoloration and subcutaneous-tissue fibrosis. The study's purpose is to determine whether skin discoloration correlates with the development of fibrosis in breast-cancer radiotherapy.Eighteen breast-cancer patients were enrolled in our initial study. All patients were previously treated with a standard course of radiation, and the median follow-up time was 22 months. The treated and untreated breasts were scanned with a spectrophotometer and an ultrasound. Two spectrophotometer parameters-melanin and erythema indices-were used to quantitatively assess skin discoloration. Two ultrasound parameters-skin thickness and Pearson coefficient of the hypodermis-were used to quantitatively assess severity of fibrosis. These measurements were correlated with clinical assessments (RTOG late morbidity scores).Significant measurement differences between the treated and contralateral breasts were observed among all patients: 27.3% mean increase in skin thickness (p < 0.001), 34.1% mean decrease in Pearson coefficient (p < 0.001), 27.3% mean increase in melanin (p < 0.001), and 22.6% mean increase in erythema (p < 0.001). All parameters except skin thickness correlated with RTOG scores. A moderate correlation exists between melanin and erythema; however, spectrophotometer parameters do not correlate with ultrasound parameters.Spectrophotometry and quantitative ultrasound are objective tools that assess radiation-induced tissue injury. Spectrophotometer parameters did not correlate with those of quantitative ultrasound suggesting that skin discoloration cannot be used as a marker for subcutaneous fibrosis. These tools may prove useful for the reduction of radiation morbidities and improvement of patient quality of life.
Project description:Acute radiodermatitis is the most common side effect in non-melanoma skin cancer patients undergoing radiotherapy. Nonetheless, despite the ongoing progress of clinical trials, no effective regimen has been found yet. In this study, a non-woven patch, comprised of electrospun polymeric micro/nanofibers loaded with an aqueous extract of <i>Pinus halepensis</i> bark (PHBE), was fabricated and clinically tested for its efficacy to prevent radiodermatitis. The bioactivity of the PHBE patch was evaluated in comparison with a medical cream indicated for acute radiodermatitis. Twelve volunteer patients were selected and randomly assigned to two groups, applying either the PHBE patch or the reference cream daily. Evaluation of radiation-induced skin reactions was performed during the radiotherapy period and 1 month afterwards according to the Radiation Therapy Oncology Group (RTOG) grading scale, photo-documentation, patient-reported outcomes (Visual Analog Scale, questionnaire), biophysical measurements (hydration, transepidermal water loss, erythema, melanin), and image analysis. In contrast with the reference product, the PHBE patch showed significant anti-inflammatory activity and restored most skin parameters to normal levels 1 month after completion of radiation therapy. No adverse event was reported, indicating that the application of the PHBE patch can be considered as a safe medical device for prophylactic radiodermatitis treatment.
Project description:To investigate the use of advanced ultrasonic imaging to quantitatively evaluate normal-tissue toxicity in breast-cancer radiation treatment.Eighteen breast cancer patients who received radiation treatment were enrolled in an institutional review board-approved clinical study. Radiotherapy involved a radiation dose of 50.0 to 50.4 Gy delivered to the entire breast, followed by an electron boost of 10.0 to 16.0 Gy delivered to the tumor bed. Patients underwent scanning with ultrasound during follow-up, which ranged from 6 to 94 months (median, 22 months) postradiotherapy. Conventional ultrasound images and radio-frequency (RF) echo signals were acquired from treated and untreated breasts. Three ultrasound parameters, namely, skin thickness, Pearson coefficient, and spectral midband fit, were computed from RF signals to measure radiation-induced changes in dermis, hypodermis, and subcutaneous tissue, respectively. Ultrasound parameter values of the treated breast were compared with those of the untreated breast. Ultrasound findings were compared with clinical assessment using Radiation Therapy Oncology Group (RTOG) late-toxicity scores.Significant changes were observed in ultrasonic parameter values of the treated vs. untreated breasts. Average skin thickness increased by 27.3%, from 2.05 ± 0.22 mm to 2.61 ± 0.52 mm; Pearson coefficient decreased by 31.7%, from 0.41 ± 0.07 to 0.28 ± 0.05; and midband fit increased by 94.6%, from -0.92 ± 7.35 dB to 0.87 ± 6.70 dB. Ultrasound evaluations were consistent with RTOG scores.Quantitative ultrasound provides a noninvasive, objective means of assessing radiation-induced changes to the skin and subcutaneous tissue. This imaging tool will become increasingly valuable as we continue to improve radiation therapy technique.
Project description:<h4>Purpose</h4> Radiation-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. <h4>Methods</h4> Patients 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. <h4>Results</h4> In 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). <h4>Conclusions</h4> The 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. <h4>Supplementary Information</h4> The online version contains supplementary material available at 10.1007/s12094-021-02729-z.
Project description:Terrestrial solar ultraviolet radiation (UVR) exerts both beneficial and adverse effects on human skin. Epidemiological studies show a lower incidence of skin cancer in people with pigmented skins compared to fair skins. This is attributed to photoprotection by epidermal melanin, as is the poorer vitamin D status of those with darker skins. We summarize a wide range of photobiological responses across different skin colours including DNA damage and immunosuppression. Some studies show the generally modest photoprotective properties of melanin, but others show little or no effect. DNA photodamage initiates non-melanoma skin cancer and is reduced by a factor of about 3 in pigmented skin compared with white skin. This suggests that if such a modest reduction in DNA damage can result in the significantly lower skin cancer incidence in black skin, the use of sunscreen protection might be extremely beneficial for susceptible population. Many contradictory results may be explained by protocol differences, including differences in UVR spectra and exposure protocols. We recommend that skin type comparisons be done with solar-simulated radiation and standard erythema doses or physical doses (J/m2 ) rather than those based solely on clinical endpoints such as minimal erythema dose (MED).
Project description:<h4>Background</h4>Almonds are a rich source of phenolic and polyphenolic compounds, which have antioxidant activity. In vitro and in vivo studies have demonstrated that topical application of almond oil and almond skin extract reduces UVB-induced photoaging. Ultraviolet-B (UVB) protection by oral almond consumption has not been previously studied in humans.<h4>Objectives</h4>To investigate whether oral almond consumption can increase resistance to UVB radiation and reduce skin aging in healthy Asian women.<h4>Methods</h4>Thirty-nine female participants (18-45 years) with Fitzpatrick skin type II-IV were randomly assigned to consume either 1.5 oz of almonds or 1.8 oz of pretzels daily for 12 weeks. Minimal erythema dose (MED) was determined using a standardized protocol, which determined the minimal radiation needed to induce erythema on the inner arm following UVB exposure. Facial skin texture was evaluated by two dermatologists using the Clinician's Erythema Assessment scale and Allergan Roughness scale. Facial melanin index, hydration, sebum, and erythema were determined using a cutometer.<h4>Results</h4>The MED was increased in the subjects consuming almonds compared to the control group consuming pretzels. There were no differences noted between the groups consuming almonds versus pretzels in Allergan roughness, melanin, hydration, or sebum on facial skin.<h4>Conclusions</h4>Our findings suggest that daily oral almond consumption may lead to enhanced protection from UV photodamage by increasing the MED.
Project description:Amiodarone has a well-established and extensive side effect profile: pulmonary fibrosis, thyroid toxicity, corneal deposits, and skin discoloration. However, in some rare instances epididymitis/orchitis is a side effect of amiodarone. Symptoms range from testicular pain to swelling and erythema.<sup>1,2</sup> The mechanism of how this toxicity occurs is unknown. In this case report, we will discuss the case of an elderly patient who developed epididymitis and orchitis after several years of tolerating amiodarone without any adverse events. Our patient underwent a full workup with testicular ultrasound, evaluation by the urology and cardiology services. His amiodarone was discontinued with complete resolution of symptoms.<h4>Data sources</h4>A community hospital in Stratford, NJ.<h4>Study selection</h4>88 year old male patient with multiple comorbidities.<h4>Data extraction</h4>Obtaining medical records on Soarian Cerner system.<h4>Data synthesis</h4>Article analysis obtained from PubMed.
Project description:Introduction Patients undergoing adjuvant radiotherapy to the breast often experience radiation dermatitis ranging from mild erythema to moist desquamation. In post-lumpectomy patients, the axilla and inframammary fold are at an increased risk for friction dermatitis. Dermatitis can impact patients' quality-of-life and may require treatment break/cessation. Our objectives are to assess the efficacy of 3M Cavilon Barrier Film (BF) in preventing and/or delaying the onset of grade-two dermatitis and reducing patient-reported sensation scores. Methods A total of 55 patients were randomized to receive BF on the medial or lateral breast. BF was applied twice weekly during treatment. Skin toxicity was evaluated weekly by a blinded clinical investigator using the Skin Toxicity Assessment Tool (STAT) and the modified Radiation Therapy Oncology Group Visual Assessment Score (RTOG VAS). On day one, baseline photographs were taken; seven-to-ten days post-treatment, patients returned for photographs, the STAT/RTOG VAS, and patient-opinion questions in the form of the global questionnaire. Results The paired analysis found BF did not significantly reduce dermatitis either during or post-treatment. However, the unpaired analysis found significantly reduced RTOG VAS on the lateral compartment during treatment (BF:0.91 vs. Control:1.21, p = 0.0408). This difference resolved post-treatment. Additionally, BF was able to reduce pruritus (p = 0.047) on the medial components and burning sensations on the lateral components (p = 0.035). There was no significant difference between the time-to-onset or proportion of patients who developed grade-two dermatitis. Conclusion In an unpaired analysis, BF significantly reduced dermatitis on the lateral compartment during treatment. Additionally, BF significantly reduced pruritus and burning sensations. A larger study using a more reliable scoring method is required to clarify the effect of BF on radiation-associated skin toxicity.
Project description:Radiation Therapy Oncology Group (RTOG) 95-17, a Phase II trial to evaluate multicatheter brachytherapy (mCathBrachy) as the sole method of radiation therapy for Stage I-II breast cancer (BrCa), was the first cooperative group trial in North America to evaluate accelerated partial breast irradiation (APBI) and include patient-reported outcomes (PROs). This report presents the year-5 toxicity and cosmesis data.After lumpectomy and axillary dissection for invasive BrCa (tumor size <3cm with zero to three positive lymph nodes), 100 patients (pts), 98 evaluable, were treated (txed) with mCathBrachy from 1997 to 2000 with 34Gy administered twice daily in 10 high-dose-rate fractions or 45Gy in 3.5-6 days as a low-dose-rate implant to 1-2cm beyond the lumpectomy bed. The PROs and physician-reported outcomes of toxicity, cosmesis, and tx satisfaction at year-5 are reported here, defined as data submitted 54-78 months after tx.Grade (G) 1-2 skin toxicity developed in 78% of the pts and G3 in 13% (no G4). The tx effects included skin dimpling/indentation (37%), fibrosis (45%), telangiectasias (45%), skin catheter marks (54%), and symptomatic fat necrosis (15%). Breast asymmetry was reported in 73%. Rates of excellent-to-good cosmesis were similar between PROs (66%) and radiation oncologists (68%). The PROs of tx satisfaction at year-5 was 75%.RTOG 95-17 documents the year-5 skin toxicity and tx effects of mCathBrachy APBI, which are associated with PROs of good-to-excellent cosmesis and high tx satisfaction. This emphasizes the importance of PROs when assessing BrCa tx. National Surgical Adjuvant Breast and Bowel Project B39/RTOG 0413 will allow for definitive comparisons between APBI and whole breast radiation therapy.
Project description:PURPOSE: To examine the association of polymorphisms in ATM (codon 158), GSTP1 (codon 105), SOD2 (codon 16), TGFB1 (position -509), XPD (codon 751), and XRCC1 (codon 399) with the risk of severe erythema after breast conserving radiotherapy. METHODS AND MATERIALS: Retrospective analysis of 83 breast cancer patients treated with breast conserving radiotherapy. A total dose of 50.4?Gy was administered, applying 1.8?Gy/fraction within 42?days. Erythema was evaluated according to the Radiation Therapy Oncology Group (RTOG) score. DNA was extracted from blood samples and polymorphisms were determined using either the Polymerase Chain Reaction based Restriction-Fragment-Length-Polymorphism (PCR-RFL) technique or Matrix-Assisted-Laser-Desorption/Ionization -Time-Of-Flight-Mass-Spectrometry (MALDI-TOF). Relative excess heterozygosity (REH) was investigated to check compatibility of genotype frequencies with Hardy-Weinberg equilibrium (HWE). In addition, p-values from the standard exact HWE lack of fit test were calculated using 100,000 permutations. HWE analyses were performed using R. RESULTS: Fifty-six percent (46/83) of all patients developed erythema of grade 2 or 3, with this risk being higher for patients with large breast volume (odds ratio, OR?=?2.55, 95% confidence interval, CI: 1.03-6.31, p?=?0.041). No significant association between SNPs and risk of erythema was found when all patients were considered. However, in patients with small breast volume the TGFB1 SNP was associated with erythema (p?=?0.028), whereas the SNP in XPD showed an association in patients with large breast volume (p?=?0.046). A risk score based on all risk alleles was neither significant in all patients nor in patients with small or large breast volume. Risk alleles of most SNPs were different compared to a previously identified risk profile for fibrosis. CONCLUSIONS: The genetic risk profile for erythema appears to be different for patients with small and larger breast volume. This risk profile seems to be specific for erythema as compared to a risk profile for fibrosis.
Project description:MammoSite balloon brachytherapy is a relatively new technique for partial breast irradiation. The present paper focuses on the treatment planning, dosimetry, and quality assurance aspects of that treatment, based on the Radiation Therapy Oncology Group 0413 randomized prospective trial (RTOG 0413) protocol. We investigate the usefulness of evaluating implants for treatment appropriateness according to the full set of RTOG criteria as compared with the manufacturer's guidelines. We describe our methods to improve MammoSite balloon implants that would otherwise not comply with the protocol. The initially acquired computed tomography (CT) images are evaluated for tissue conformance, balloon surface-to-skin distance, and balloon symmetry. If the implant fails to meet the foregoing criteria, corrective action such as delay in the CT scan, balloon manipulation, or fluid volume adjustment is taken, and the patient is re-scanned. If the corrective action appears to be successful, three dimensional treatment planning and dose-volume histogram analysis is performed to evaluate the geometric and dosimetric parameters with regard to the RTOG 0413 protocol. The evaluated parameters include, volume ratio of the lumpectomy cavity to the ipsilateral breast, target volume coverage, tissue-balloon conformance, balloon symmetry, minimal balloon surface-to-skin distance, maximum skin dose, and normal breast tissue dose-volume parameters V150 and V200. Among our implants, 21.7% did not initially meet the RTOG 0413 acceptance criteria. Asymmetry and poor conformance values reduce the target volume coverage, and so an implant with moderate conformance and asymmetry can be within the manufacturer's guidelines, but still not meet the RTOG criteria. Our intervention corrected all but one of the implants that failed to meet the criteria. Manipulating the cavity and adjusting the balloon volume may salvage an implant and meet the strict geometric and dosimetric criteria imposed by the RTOG 0413 protocol.