Irradiated Skin Areas Research Articles

Therapeutic Potential of Hydrogen as a Radioprotective Agent for the Prevention of Radiation Dermatitis

Radiation dermatitis (RD) is a common side effect in patients receiving radiotherapy. Currently, clinical skincare approaches for acute RD vary widely among institutions and lack consensus. Hydrogen molecules, acting as radioprotective agents by selectively scavenging free radicals, have the potential to protect against RD. In this study, we demonstrate that hydrogen reduces double-strand breaks, mitochondrial depolarization, and inflammatory cytokines induced by irradiation damage in HaCaT cells. Furthermore, in vivo experiments reveal that exposing irradiated skin areas to a hydrogen gas environment alleviates RD. Assessment of skin appearance grade and histology staining revealed that direct transdermal application of hydrogen can prevent radiation-induced follicle damage, dermal thickening, and leukocyte infiltration, thereby reducing the severity of RD. In addition, hydrogen enhances the skin’s antioxidant capacity, leading to a reduction in the Bcl-2-associated X protein/B-cell lymphoma 2 (Bax/Bcl-2) ratio, the number of apoptotic cells, and the expression of pro-inflammatory cytokines. Our data demonstrate that hydrogen possesses antioxidant, anti-inflammatory, and anti-apoptotic properties, and could be a preventive strategy for RD.

Alleviation of Severe Skin Insults Following High-Dose Irradiation with Isolated Human Fetal Placental Stromal Cells.

Skin exposure to high-dose irradiation, as commonly practiced in radiotherapy, affects the different skin layers, causing dry and wet desquamation, hyperkeratosis fibrosis, hard to heal wounds and alopecia and damaged hair follicles. Fetal tissue mesenchymal stromal cells (f-hPSC) were isolated from excised human fetal placental tissue, based on their direct migration from the tissue samples to the tissue dish. The current study follows earlier reports on for the mitigation of acute radiation syndrome following whole body high-dose exposure with remotely injected f-hPSC. Both the head only and a back skin flap of mice were irradiated with 16 &18 Gy, respectively, by 6MeV clinical linear accelerator electron beam. In both locations, the irradiated skin areas developed early and late radiation induced skin damages, including cutaneous fibrosis, lesions, scaring and severe hair follicle loss and reduced hair pigmentation. Injection of 2 × 106 f-hPSC, 3 and 8 weeks following 16 Gy head irradiation, and 1 and 4 weeks following the 18 Gy back skin only irradiation, resulted in significantly faster healing of radiation induced damages, with reduction of wet desquamation as measured by surface moisture level and minor recovery of the skin viscoelasticity. Detailed histological morphometry showed a clear alleviation of radiation induced hyperkeratosis in f-hPSC treated mice, with significant regain of hair follicles density. Following 16 Gy head irradiation, the hair follicles density in the scalp skin was reduced significantly by almost a half relative to the controls. A nearly full recovery of hair density was found in the f-hPSC treated mice. In the 18 Gy irradiated back skin, the hair follicles density dropped in a late stage by ~70% relative to naïve controls. In irradiated f-hPSC treated mice, it was reduced by only ~30% and was significantly higher than the non-treated group. Our results suggest that local injections of xenogeneic f-hPSC could serve as a simple, safe and highly effective non-autologous pro-regenerative treatment for high-dose radiation induced skin insults. We expect that such treatment could also be applied for other irradiated organs.

Radiation-irritated skin and hyperpigmentation may impact the quality of life of breast cancer patients after whole breast radiotherapy

BackgroundThis study aimed to investigate skin condition, quality of life, and psychological impact of breast cancer patients after radiation therapy. We designed and administered a questionnaire to breast cancer survivors for better understanding the skin sequelae after radiation therapy.MethodsThis study performed an anonymous online survey. Invitation join was posted in Facebook groups for Breast Cancer. Content of the questionnaire included basic information and a three-point scale on the degree of skin dryness, sweating, hotness sensation, itchy sensation, presence of pigment deposition, history of severe skin disorder, psychological impact, and quality of life after radiotherapy. Categorical variables were summarized using counts and percentages, and then Mantel–Haenszel chi-square tests, multiple correspondence analysis, Wald chi-square statistics, and logistic regression analyses were performed; P < 0.05 was considered statistically significant.ResultsIn total, 421 breast cancer survivors completed the questionnaire. Among them, 331 (78.62%) reported rarely sweating; 340 (80.76%) reported dry skin; 184 (43.71%) reported itchy skin in addition to dry skin; 336 (79.81%) had severe or mild skin color deposition; and 76 (18.05%) had eczema or contact dermatitis. Dry skin problems were caused by absent sweating and skin dryness in the irradiated skin area, post-RT severe skin disorders, and skin color deposition. Compared with patients sweating normally in the radiation field, patients with absent sweating and hotness sensation in the radiation field had a higher risk of depression.ConclusionsThis study showed that breast cancer patients after whole breast radiotherapy may experience skin dryness, hypersensitivity and hyper pigmentation in the irradiated skin area. These “radiation-irritated skin” lesions may induce depressive psychological status and impact the quality of life in breast cancer patients after whole breast radiotherapy.

Abstract 5349: Proton FLASH radiation spares normal skin and soft tissues of the murine leg from radiation-induced damage while being equipotent with standard proton radiation in controlling sarcoma growth

Abstract Purpose: To investigate the potential normal tissue sparing effects of proton FLASH radiation on skin injury, leg contraction, and soft tissue inflammation while maintaining tumor cell killing efficacy for orthotopic murine fibrosarcoma tumor. Materials and Methods: C3H/HeJ and C57BL/6J mice (n= 6) received 45 Gy of proton FLASH (&amp;gt;85Gy/sec) or conventional radiation (CONV) (1Gy/sec), at the right hind leg. Normal tissue responses were evaluated by recording the skin reaction and the leg contraction over time as acute and chronic macroscopic observations of radiation-induced damage. The skin reactions were recorded using a scoring system of 10 grades, ranging from 0.5 to 3.5, with breakdown of irradiated skin area with moist exudate to be defined as 3. Leg contraction assay examined the extensibility of the leg using a jig and leg contracture was defined as the difference in length between the irradiated and non-irradiated hind leg. Neutrophil infiltration, measured by myeloperoxidase (MPO) activity, and persistent inflammation have been associated with the development of fibrosis, as a long-term effect post radiation. MPO activity was quantified by using intravenously administered luminol and chemiluminescence IVIS imaging at several time points post radiation. We also compared the antitumor efficacy of proton Flash radiation with Proton Standard radiation using syngeneic mice bearing orthotopic fibrosarcoma tumors on the hind leg. Tumors were established by intramuscularly injecting radiation-induced fibrosarcoma (RIF) cells in C57BL/6J mice. Tumor growth was monitored by tumor volume measurements, using a caliper. Results: Acute effects of radiation on skin began with erythema, edema, pigment changes and depilation and was followed by complete loss of the epidermis, constant fibrinous exudates and edema. Skin reaction of C3H/HeJ mice exposed to proton FLASH radiation blindly received a 60% lower score than the CONV-irradiated mice at day 24 post IR, whereas C57BL/6J mice received 60% lower score at day 39, as they appear to be more radiosensitive. Leg contracture was clearly observed by day 68 in the C3H/HeJ whereas in C57BL/6J appeared much earlier, at 10 days post-radiation. Proton FLASH-irradiated group of C57BL/6J mice presented 50% less leg contracture as compared to the CONV-irradiated group, by day 46. MPO activity peaked for both strains at day 18 post radiation and FLASH-irradiated mice showed significantly higher levels of MPO activity compared to the CONV-irradiated mice. The MPO activity was still significantly different between proton FLASH and CONV groups up to day 27 in C57BL/6J mice. Moreover, proton FLASH and CONV radiation inhibited fibrosarcoma tumor growth to the same extent, and there was no significant difference in tumor growth delay or overall survival between the two groups. Conclusions: Proton FLASH radiation causes significant less skin and soft tissue injury as well as lower levels of inflammation post-radiation compared to proton CONV radiation whereas tumor growth inhibition is indistinguishable between the two modalities. Citation Format: Anastasia Velalopoulou, Ilias V. Karagounis, Ioannis I. Verginadis, Denisa Goia, Michele Kim, Khayrullo Shoniyozov, Keith Cengel, Eric Diffenderfer, Lei Dong, James Metz, Theresa Busch, Amit Maity, Costas Koumenis. Proton FLASH radiation spares normal skin and soft tissues of the murine leg from radiation-induced damage while being equipotent with standard proton radiation in controlling sarcoma growth [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5349.

Radiation-induced angiosarcoma of the breast: A review.

Angiosarcoma is a rare, aggressive malignant vascular neoplasm with poor prognosis that has a predilection for skin and superficial soft tissue. It can arise spontaneously or in association with factors like chronic lymphedema or radiation therapy. Radiotherapy used to treat invasive breast tumors is a known risk factor for the development of the so-called radiation-induced angiosarcoma (RIAS), a condition that has been described in the literature with increasing frequency. Radiation-induced angiosarcoma of the breast usually arises on the previously irradiated skin area several years after radiotherapy and presents as painless multifocal erythematous patches or plaques similar to a hematoma. Cutaneous biopsy is essential for the diagnosis. Histologically, RIAS is characterized by irregular anastomosing vessels lined by endothelial cells showing nuclear atypia. Treatment is mostly surgical, and mastectomy with negative margins is considered the standard procedure. However, recurrences are common, and an approach combining surgery, chemo- and radiotherapy may be more effective. The purpose of this study is to review the most recent medical literature on RIAS of the breast, with emphasis on its pathophysiology, clinical and histological features and current treatment options.

Discrepancies between cortical and behavioural long-term readouts of hyperalgesia in awake freely moving rats.

BackgroundIt is still unclear to what extent the most common animal models of pain and analgesia, based on indirect measures such as nocifensive behaviours, provide valid measures of pain perception.MethodsTo address this issue, we developed a novel animal model comprising a more direct readout via chronically (>1 month) implanted multichannel electrodes (MCE) in rat primary somatosensory cortex (S1; known to be involved in pain perception in humans) and compared this readout to commonly used behavioural pain‐related measures during development of hyperalgesia. A translational method to induce hyperalgesia, UVB irradiation of the skin, was used. Localized CO 2 laser stimulation was made of twenty skin sites (20 stimulations/site/observation day) on the plantar hind paw, before and during the time period when enhanced pain perception is reported in humans after UVB irradiation.ResultsWe demonstrate a 2–10 fold significant enhancement of cortical activity evoked from both irradiated and adjacent skin and a time course that corresponds to previously reported enhancement of pain magnitude during development of primary and secondary hyperalgesia in humans. In contrast, withdrawal reflexes were only significantly potentiated from the irradiated skin area and this potentiation was significantly delayed as compared to activity in S1.ConclusionsThe present findings provide direct evidence that chronic recordings in S1 in awake animals can offer a powerful, and much sought for, translational model of the perception of pain magnitude during hyperalgesia.What does this study add? In a novel animal model, chronic recordings of nociceptive activity in primary somatosensory cortex (S1) in awake freely moving rats are compared to behavioural readouts during UVB‐induced hyperalgesia. Evoked activity in rat S1 replicates altered pain perception in humans during development of hyperalgesia, but withdrawal reflexes do not.

Effect of mesenchymal stem cells and platelet-derived growth factor on the healing of radiation induced ulcer in rats.

Radiation-induced skin ulceration is a frequent complication of radiation therapy. This study investigated the effects of rat mesenchymal stem cells (rMSCs) and platelet-derived growth factor (PDGF) on the healing of radiation-induced soft tissue injury. Sprague-Dawley rats (n=17) were irradiated on the right and left buttocks with a single dose of 50 Gy. The right buttocks were administered with phosphatebuffered solution as a control. The left buttocks were administered with either rMSCs (2×106 cells), PDGF (8 µg), or PDGF combined with rMSCs. Administration was done at three weeks after irradiation. Wound healing was analyzed by calculating the percentage of residual ulcerated skin area compared to the total irradiated area during the five week healing period after administration. Modified skin scores were also assessed. Finally, skin lesions were histologically evaluated. More than 40% of the irradiated skin area within the irradiated zone underwent ulceration within 16 days postirradiation, with peak ulceration exceeding 50% around three weeks post-irradiation. Administration of rMSCs or PDGF alone did not confer any significant healing effect. The combined rMSCs+PDGF treatment significantly reduced the wound size compared with the nontreated control up to two weeks postinjection. Regarding the histological examination, lesions administered with PDGF (either alone or mixed with rMSCs) resulted in a greater deposition of highly organized collagen fibers throughout the dermis layer, compared with the control. In conclusion, the combined administration of rMSCs and PDGF efficiently enhanced the healing of radiation-induced skin ulceration.

Interaction between ultraviolet B-induced cutaneous hyperalgesia and nerve growth factor-induced muscle hyperalgesia.

Clinical observations indicate that cutaneous hyperalgesia may arise from pain located in deep structures. The objective of this study was to investigate whether combined sensitization of deep and superficial somatic tissues facilitates skin hyperalgesia. The interaction between muscle and cutaneous hyperalgesia was investigated in 16 healthy volunteers. Skin sensitization was induced unilaterally on the same randomly selected part of the body by ultraviolet B (UVB) irradiation above the upper trapezius and low back muscles. The next day, muscle hyperalgesia was induced bilaterally in low back muscles by injections of nerve growth factor (NGF). Thus, 1day after irradiation there was skin sensitization, whereas after 2days both skin and muscle sensitizations were present. Cutaneous blood flow, pin-prick thresholds, pressure pain thresholds (PPTs), temporal summation to repetitive painful pressure stimulation, and stimulus-response functions of graded pressure stimulations and pain intensity were assessed within the irradiated skin area and in the surrounding area before and 1, 2 and 3days after irradiation. Comparing baseline with 1day after irradiation, UVB and UVB+NGF locations demonstrated: (1) Increased superficial blood flow inside the irradiated area (p<0.01); (2) Reduced pin-prick (p<0.01) and PPTs (p<0.05) within the irradiated area and in the surrounding area; (3) Left-shifted pressure stimulus-response function within the irradiated area (p<0.01); (4) Facilitated temporal summation inside the irradiated area (p<0.01). Using skin and deep tissue pain sensitization models simultaneously, no significant synergistic effects were found within the 3-day investigation suggesting little integration between the two phenomena in this period.

Hyperalgesia and allodynia to superficial and deep-tissue mechanical stimulation within and outside of the UVB irradiated area in human skin

Background and aimsThe ultraviolet-B (UVB) inflammatory model is a well-established model of inflammatory pain. This study investigated whether UVB-induced cutaneous inflammation would enhance pain responses from the underlying deep somatic areas. MethodsSkin inflammation was induced, in 24 healthy volunteers, by UVB irradiation (three times of the individual minimal erythema UVB dose) in square-shaped areas on the forearm and lower back. Assessments of cutaneous blood flow, pin-prick thresholds, pressure pain thresholds and tolerance, stimulus–response functions relating graded pressure stimulations and pain intensity (visual analogue scale, VAS) were performed within and outside the irradiated area. ResultsTwenty-four hours after UVB irradiation, a significant increase in superficial blood flow in the irradiated skin area was demonstrated compared with baseline (P<0.01) indicating that inflammation was induced. Compared with baseline, UVB irradiation significantly reduced the pin-prick thresholds, pressure pain thresholds and tolerance within and outside of the irradiated area (P<0.05). The stimulus–response function was left-shifted compared with baseline both within and outside the irradiated area (P<0.05) with a more pronounced left-shift within the irradiated area (P<0.01). Application of topical anaesthesia 24h after irradiation in 5 subjects, both within and outside the irradiated area, could only increase the pin-prick thresholds outside the irradiated area. ConclusionThe UVB irradiation of the skin not only provokes cutaneous primary and secondary hyperalgesia but also causes hyperalgesia to blunt pressure stimulations 24h after the UVB exposure. ImplicationsThe presented UVB model can be used as a translational model from animals into healthy subjects. This model can potentially be used to screen drug candidates with anti-inflammatory properties in early stages of drug development.

Radiation dermatitis, burns, and recall phenomena: Meaningful instances of immunocompromised district

Ionizing and ultraviolet radiations, as well as burns, can selectively damage and immunologically mark the cutaneous area they act on through direct and indirect mechanisms. After the causal event has disappeared, the affected skin district may appear clinically normal, but its immune behavior is often compromised forever. In fact, irradiated or burned skin areas undergo a destabilization of the immune control, which can lead to either a reduction of immunity (as suggested by the facilitated local occurrence of tumors and infections) or an excess of it (as suggested by the possible local onset of disorders with exaggerated immune response). In other words, these areas become typical immunocompromised districts (ICD). Also, in recall phenomena the damaged skin area usually behaves as an ICD with an exaggerated immune response toward a wide range of drugs (especially chemotherapeutic agents) that prove to be harmless on the undamaged skin surface.The occurrence of any skin disorder on an irradiated, photoexposed, or burned skin area can be defined as an isoradiotopic, isophototopic, or isocaumatopic response, respectively; however, the opposite may also occur when elsewhere generalized cutaneous diseases or eruptions selectively spare irradiated, photoexposed, or burned skin sites (isoradiotopic, isophototopic, and isocaumatopic nonresponse, respectively). The pathomechanisms involved in any secondary disorder occurring on irradiated or burned skin areas may be linked to locally decreased or altered lymph flow (with dysfunction of lymph drainage) on the one hand, and to fibrotic throttling or reduction of peptidergic nerve fibers (with dysfunction of neuroimmune signaling) on the other hand, resulting in a significant dysregulation of the local immune response. Future clinical observations and experimental investigations on radiation dermatitis, sunburns, and thermal or chemical skin injuries should shed new light on the mechanisms regulating regional resistance to infectious agents, local oncogenesis, and district propensity to dysimmune reactions.

Increased skin and mucosal toxicity in the combination of vemurafenib with radiation therapy

Palliative radiotherapy is often required for patients with metastatic malignant melanoma in the case of bone or brain metastases. Since BRAF inhibitor therapy is highly efficient in V600-mutated melanomas, there is hesitation to stop it during radiotherapy. Consequently, radiotherapy under simultaneous vemurafenib treatment is frequently needed. We report the case of a patient receiving palliative radiotherapy of spinal bone metastases before and during vemurafenib therapy. The skin reactions were quantitatively scored using computer-assisted digital image evaluation. Radiotherapy without vemurafenib was tolerated very well, whereas radiotherapy under simultaneous vemurafenib treatment resulted in accentuated skin reactions. Furthermore, the patient developed dysphagia and had to be hospitalized for parenteral nutrition. In the quantitative analysis, there was a twofold increase in pigmentation and erythema of the irradiated skin area of the thoracic spine when vemurafenib was combined with radiotherapy compared with radiotherapy treatment alone. This is the first reported case of a patient showing no complications during radiotherapy without vemurafenib but remarkable skin and mucosal toxicity under concurrent vemurafenib therapy. Thus, a genetically conditioned individually elevated radiosensitivity can definitely be excluded. Compared with other reported cases, radiosensitization was not limited to the skin, but also affected the esophageal mucosa. Vemurafenib is a strong radiosensitizer. Patients receiving radiotherapy under simultaneous vemurafenib treatment should be monitored very closely.

In vivo analysis of THz wave irradiation induced acute inflammatory response in skin by laser-scanning confocal microscopy.

The recent development of THz sources in a wide range of THz frequencies and power levels has led to greatly increased interest in potential biomedical applications such as cancer and burn wound diagnosis. However, despite its importance in realizing THz wave based applications, our knowledge of how THz wave irradiation can affect a live tissue at the cellular level is very limited. In this study, an acute inflammatory response caused by pulsed THz wave irradiation on the skin of a live mouse was analyzed at the cellular level using intravital laser-scanning confocal microscopy. Pulsed THz wave (2.7 THz, 4 μs pulsewidth, 61.4 μJ per pulse, 3Hz repetition), generated using compact FEL, was used to irradiate an anesthetized mouse's ear skin with an average power of 260 mW/cm(2) for 30 minutes using a high-precision focused THz wave irradiation setup. In contrast to in vitro analysis using cultured cells at similar power levels of CW THz wave irradiation, no temperature change at the surface of the ear skin was observed when skin was examined with an IR camera. To monitor any potential inflammatory response, resident neutrophils in the same area of ear skin were repeatedly visualized before and after THz wave irradiation using a custom-built laser-scanning confocal microscopy system optimized for in vivo visualization. While non-irradiated control skin area showed no changes in the number of resident neutrophils, a massive recruitment of newly infiltrated neutrophils was observed in the THz wave irradiated skin area after 6 hours, which suggests an induction of acute inflammatory response by the pulsed THz wave irradiation on the skin via a non-thermal process.

Mechanism and biological relevance of blue-light (420–453 nm)-induced nonenzymatic nitric oxide generation from photolabile nitric oxide derivates in human skin in vitro and in vivo

Human skin contains photolabile nitric oxide (NO) derivates such as nitrite and S-nitrosothiols, which upon UVA radiation decompose under high-output NO formation and exert NO-specific biological responses such as increased local blood flow or reduced blood pressure. To avoid the injurious effects of UVA radiation, we here investigated the mechanism and biological relevance of blue-light (420–453nm)-induced nonenzymatic NO generation from photolabile nitric oxide derivates in human skin in vitro and in vivo. As quantified by chemiluminescence detection (CLD), at physiological pH blue light at 420 or 453nm induced a significant NO formation from S-nitrosoalbumin and also from aqueous nitrite solutions by a to-date not entirely identified Cu1+-dependent mechanism. As detected by electron paramagnetic resonance spectrometry in vitro with human skin specimens, blue light irradiation significantly increased the intradermal levels of free NO. As detected by CLD in vivo in healthy volunteers, irradiation of human skin with blue light induced a significant emanation of NO from the irradiated skin area as well as a significant translocation of NO from the skin surface into the underlying tissue. In parallel, blue light irradiation caused a rapid and significant rise in local cutaneous blood flow as detected noninvasively by using micro-light-guide spectrophotometry. Irradiation of human skin with moderate doses of blue light caused a significant increase in enzyme-independent cutaneous NO formation as well as NO-dependent local biological responses, i.e., increased blood flow. The effects were attributed to blue-light-induced release of NO from cutaneous photolabile NO derivates. Thus, in contrast to UVA, blue-light-induced NO generation might be therapeutically used in the treatment of systemic and local hemodynamic disorders that are based on impaired physiological NO production or bioavailability.

Vemurafenib and Radiosensitization

The BRAF inhibitor, vemurafenib, was recently approved for the treatment of patients with BRAFV600 metastatic melanoma. Wider use of this drug and longer follow-up periods of treatment are resulting in the emergence of a growing number of reports detailing new adverse effects. Cutaneous adverse effects are preeminent with UV-A-dependent phototoxicity, hyperkeratotic folliculitis, hand-foot skin reaction, hair changes, verrucous papillomas, keratoacanthomas, and squamous cell carcinomas. We report 2 cases of dermatitis occurring on a previously irradiated skin area in patients treated with vemurafenib for a BRAFV600-mutated metastatic melanoma. The first case occurred 10 days after a low dose of radiation was delivered that usually does not induce any radiodermatitis, suggesting radiosensitization by vemurafenib. The second case occurred 30 days after radiotherapy and was diagnosed as radiation recall dermatitis. Vemurafenib should be considered a potential cutaneous radiosensitizer and an inducer of radiation recall dermatitis. However, these adverse effects are easily managed with topical corticosteroids. Dose reduction or interruption of vemurafenib is not required. Further studies and reports will enlighten us as to whether this pharmacodynamic interaction between x-rays and vemurafenib is also seen with other BRAF or MEK inhibitors on the same mitogen-activated protein kinase pathway currently under development.

SU-E-T-277: Modeling Normal Tissue Complication Probability Based On Compiled Clinical Data From Skin Cancer Radiotherapy

Purpose: Our objective is to model normal tissue complication probability (NTCP) based on published clinical data of head/face non‐melanoma skin cancers to determine optimum treatment schemes using advanced radiotherapy (RT) technologies. Methods: Reports citing crude estimates of erythema, desquamation and telangiectasia for primary basal and squamous cell carcinoma (BCC & SCC, resp) of the head/face were used in model development. The models had the form: NTCP = 1/(1+exp(‐(BED + BEDprolif x T — TD50)/k), where BED is the LQ model based biological effective dose. Uncomplicated tumor control functions (UCTCs) were created using NTCP models together with our own separately published TCP models. Values of BED maximizing UCTC were calculated and compared with 5 × 7.2 Gy in one week and 15 × 3 Gy in 3 weeks treatment schedules (BED 14 = 54.5 & 54.6 Gy, respectively). Results: Literature search yield six reports useful in the development of a TCP model for BCC/SCC. The reported a median total dose of 39.0 Gy (range: 23.9–52.4 Gy), dose per fraction of 3.3 Gy/fx (range: 1.7–7.3 Gy/fx), & total treatment time of 28.7 days (range: 12–40 days). Three NTCP and 12 UTCP models were generated for treatments with tumors of size 2cm. Maximum UCTC occurred at biological effective doses (BEDs) ranging from 36.25–52.25 Gy to the BCC/SCC tumors 2 cm in size. Conclusion: Three NTCP models for endpoints observed in skin cancer RT were developed based on published data, which can depend on the size of irradiated skin area (future work will explore the area–NTCP relationship further). BED values for single and multiple fraction treatments were identified to maximize UCTC for tumors > 2 cm in size, though smaller tumors may benefit from treatment schedules with lower BED.

An athymic rat model of cutaneous radiation injury designed to study human tissue-based wound therapy.

PurposeTo describe a pilot study for a novel preclinical model used to test human tissue-based therapies in the setting of cutaneous radiation injury.MethodsA protocol was designed to irradiate the skin of athymic rats while sparing the body and internal organs by utilizing a non-occlusive skin clamp along with an x-ray image guided stereotactic irradiator. Each rat was irradiated both on the right and the left flank with a circular field at a 20 cm source-to-surface distance (SSD). Single fractions of 30.4 Gy, 41.5 Gy, 52.6 Gy, 65.5 Gy, and 76.5 Gy were applied in a dose-finding trial. Eight additional wounds were created using the 41.5 Gy dose level. Each wound was photographed and the percentage of the irradiated area ulcerated at given time points was analyzed using ImageJ software.ResultsNo systemic or lethal sequelae occurred in any animals, and all irradiated skin areas in the multi-dose trial underwent ulceration. Greater than 60% of skin within each irradiated zone underwent ulceration within ten days, with peak ulceration ranging from 62.1% to 79.8%. Peak ulceration showed a weak correlation with radiation dose (r = 0.664). Mean ulceration rate over the study period is more closely correlated to dose (r = 0.753). With the highest dose excluded due to contraction-related distortions, correlation between dose and average ulceration showed a stronger relationship (r = 0.895). Eight additional wounds created using 41.5 Gy all reached peak ulceration above 50%, with all healing significantly but incompletely by the 65-day endpoint.ConclusionsWe developed a functional preclinical model which is currently used to evaluate human tissue-based therapies in the setting of cutaneous radiation injury. Similar models may be widely applicable and useful the development of novel therapies which may improve radiotherapy management over a broad clinical spectrum.

Treatment of radiation-induced mucocutaneous toxicity

During radiotherapy 80% to 90% of all patients will develop some degree of inflammation symptoms, such as erythema, dry or wet desquamation, skin folds, or mucositis depending on radiation-and patient-related factors and the extent of irradiated skin or mucosal areas. Up to now radiation induced local reactions represent still an important toxicity factor. Cutaneous and mucosal side effects may reduce the patient's compliance and can be limiting factors to follow radiotherapy protocols. Therefore, there is a high need for effective prophylactic and therapeutic treatments. Basically, guidelines recommend the avoidance of mechanical, chemical and thermal irritants, especially the exposure to high temperatures. To delay onset of radiodermatitis various preventive topicals may be applied like aqueous cream formula with or without antioxidative agents. In general, the treatment of radiodermatitis primarily should maintain moisture and skin permeability and consists of hydrophilic creams, antioxidative and anti-inflammatory topicals. Hydrocolloid dressings may reduce and improve wound healing in grade 2 and 3 reactions. Supportive therapy of radiation-induced mucositis includes the maintenance of oral care protocols and adequate nutrition during the course of treatment. A sufficient oral health status is one of the most important factors for prevention of severe oral complications. The MASCC guidelines recommend furthermore the use of non-medicated rinses with saline or sodium bicarbonate 4 to 6 times daily. Further approaches suggest the use of local anaesthetics and systemic analgesics for severe mucositis. Besides local preventive agents and supportive care protocols, modern radiation treatment techniques remain the most promising intervention in reducing the degree of skin reactions.

Transcriptional signatures of full‐spectrum and non‐UVB‐spectrum solar irradiation in human skin

Transcriptional signatures of full‐spectrum and non‐UVB‐spectrum solar irradiation in human skin

A diffuse reflectance spectroscopic study of UV-induced erythematous reaction across well-defined borders in human skin

The colour of tissue is often of clinical use in the diagnosis of tissue homeostasis and physiological responses to various stimuli. Determining tissue colour changes and borders, however, often poses an intricate problem and visual examination, constituting clinical praxis, does not allow them to be objectively characterized or quantified. Demands for increased inter- and intra-observer reproducibility have been incentives for the introduction of objective methods and techniques for tissue colour (e.g. erythema) evaluation. The aim of the present paper was to study the border zone of a UVB-provoked erythematous response of human skin in terms of blood volume and oxygenation measured by means of diffuse reflectance spectroscopy using a commercial probe. A provocation model, based on partial masking of irradiated skin areas, defines two erythema edges at every skin site responding to the UV irradiation. In every subject, five test sites were exposed with a constant UV light irradiance (14 mW/cm(2)), but with different exposure times (0, 3, 6, 9 and 12 s). An analysis of the spectral data measured across the two edges was performed for every scan line. The oxygenized and deoxygenized haemoglobin contents were estimated in every measurement point, using a modified Beer-Lambert model. The fit of the experimental data to the model derived by the modified Beer-Lambert law was excellent (R(2)>0.95). Analysing data for the chromophore content showed that the erythematous response in the provoked areas is dominated by the increase in oxyhaemoglobin. The widths for the left and right border zone were estimated to be 1.81+/-0.93 and 1.90+/-0.88 mm, respectively (mean+/-SD). The unprovoked area between the two edges was estimated to be 0.77+/-0.68 mm. While the chosen data analysis performed satisfactorily, the ability of the probe design to differentiate the spatial aspects of a reaction with abrupt borders was found to be suboptimal resulting in a probable overestimation of the erythematous edge slope. Probe modification or imaging techniques are possible solutions.

Use of deodorants during adjuvant breast radiotherapy: A survey of compliance with standard advice, impact on patients and a literature review on safety

Proscription of antiperspirant or deodorant use during adjuvant breast radiotherapy is common. The investigators were seeking an information base to facilitate design of an appropriate controlled trial of the use of deodorants during radiotherapy. The first component consisted of a survey of women after adjuvant breast radiotherapy seeking information about routine deodorant use and potential concern if deodorants were not permitted during radiotherapy. The second component comprised a literature search for any existing controlled evidence regarding harm from deodorant use during radiotherapy. Four hundred fourteen women completed surveys. Two hundred eighty recalled advice against deodorants. Two hundred ninety-nine women routinely used deodorants, 70% of whom used roll-on products. Forty-five continued deodorant use during radiation, 20 of these despite recalling advice not to wear a deodorant. Of the 233 women who routinely wore a deodorant but abstained during radiotherapy, 19% expressed a lot of concern about body odour and 45% were slightly concerned. Three controlled studies totalling 310 patients report specific deodorants versus no deodorant use which did not show statistically significantly increased skin reactions, but had only a small subset with axillary irradiation. The proscription of deodorant use during radiotherapy is of unproven benefit and causes body odour concern to the majority of women who are usual deodorant users. The next most appropriate trial would compare use of the usual deodorant versus no deodorant, would encompass a significant number of women with radiotherapy to the axilla or application of deodorant to irradiated skin areas, and include endpoints other than skin reaction alone.