The intent of radiotherapy is on destroying cancer cells however, it does not give regard to healthy body cells. Unstable atoms and subatomic particulate emitted from radiotherapy interact with electrons in the tissue, resulting in a cascade effect that leads to damage of the DNA in multiple body systems. The integumentary (skin) system is a rapidly proliferating tissue and is commonly in the direct path of radiotherapy treatment. Therefore, damage to the skin structures are common side effects of radiotherapy treatment. Skin complications are reported in 30% of breast cancer patients and may occur decades after cessation of treatment.
Radiotherapy alters processes in the skin by affecting the synthesis, maturation and function of growth factors, cytokines and metalloproteases. Immune cells infiltrate the site of irradiation to attempt to repair the damaged tissue, unresolved damage later manifests as mutations in cellular functions. The extent of damage differs depending on dosage, frequency and individual health status.
There are three reported phases that are consistent on healthy tissue following radiation.
1. The acute phase damages germinative cells in the epidermis and skin appendages.
The onset of acute damage may take two to six months to manifest, resolution often occurs upon cessation of radiotherapy. However, as the nature of radiotherapy requires patients to undergo a course of treatments, the subsequent interruption of the wound repair process of already irradiated tissue causes an amplified inflammatory response. Repetitive injury to the tissue has detrimental effects. Adverse cutaneous expressions such as radiodermatitis, erythema, oedema and lesion manifestation may even delay subsequent radiotherapy and reconstructive procedures.
2. The second phase is termed the “symptom-free latency phase” and is dose dependent, manifestations of damage may evolve months to years later.
3. The later and chronic phase of radiotherapy is shown to be irreversible and progressive.
A decrease in oxygen binding organelles results in less healing capability and endothelial cell dysfunction. Additionally, radiotherapy causes a dysregulation of growth factors and collagen disruption. Vascular endothelial growth factor (VEGF), fibroblast growth factors (FGF) and collagen type I and III are critical components of endothelial cells and vasculature. Consequently, deposits of calcium phosphate in the mitochondria of the cell alter cellular respiration and induce cell apoptosis. An altered regulation of these processes leads to ischaemia and weakened tissue which decreases the tensile strength of the skin and may later lead to ulceration.
Furthermore, chronic injury to deeper dermal structures initiates changes to the hair matrix resulting in permanent alopecia and slowed hair growth. Interestingly, anagen growth stage hairs are more affected by initial radiotherapy in contrast to the telangen matrix cells, which store radiation for a period of time. These findings support later manifestations of cutaneous reactions years after radiotherapy. This is significant as germinative cells in the hair bulge contribute to neo-epidermis in the later stages of wound repair and may affect the recovery following breast reconstruction.
Regardless of visual and palpable cutaneous reactions, there is also a significant correlation between fibrosis in irradiated breast tissue when compared to the non-irradiated breast, showing an average increase in tissue thickness of 32%. The earlier destruction of delicate vasculature and hypovascularisation contribute to fibrosis formation following the development of dystrophic calcification. These findings can be measured by ultrasonographic images and are seen in patients without palpable or visual fibrosis.
Radiotherapy effects on the skin are highly dependent on dosage, frequency and baseline health of the patient. In the recent years skin disturbances have decreased with the increase in precision when administrating radiotherapy. Radiotherapy is shown to be very effective at reducing the tumor size resulting in less excision of tissue.
The next blog will descibe a common breast reconstruction technique using fat, muscle and skin from the lower abdomen.
Marnina Diprose holds a Bachelor Health Science in Dermal Therapies, a Diploma of Beauty Therapy and a Vocational Certificate of Laser and Light. Marnina has a strong passion in scar revision and holistic approaches to patient care. For media inquiries or if you have an interest in blog contribution please email email@example.com
Bégon, E., Blum, L., Petitjean, B., Bleichner, O., Vautier, S., Huguet, F., & Bachmeyer, C. (2014). Symptomatic dystrophic cutaneous calcification as a late complication of radiotherapy for breast cancer. International Journal Of Dermatology, 53(11), 542-544.
Dormand, E., Banwell, P., & Goodacre, T. (2005). Radiotherapy and wound healing. Int Wound Journal, 2(2), 112-127.
Garcin, C., Ansell, D., Headon, D., Paus, R., & Hardman, M. (2016). Hair Follicle Bulge Stem Cells Appear Dispensable for the Acute Phase of Wound Re-epithelialization. STEM CELLS, 34(5), 1377-1385.
Haubner, F., Ohmann, E., Pohl, F., Strutz, J., & Gassner, H. (2012). Wound healing after radiation therapy: Review of the literature. Radiation Oncology, 7(1), 162.
Khoshbin, A., Mohamadabadi, F., Vafaeian, F., Babania, A., Akbarian, S., & Khandozi, R. et al. (2015). The effect of radiotherapy and chemotherapy on osmotic fragility of red blood cells and plasma levels of malondialdehyde in patients with breast cancer. Reports Of Practical Oncology & Radiotherapy, 20(4), 305-308.
Landoni, V., Giordano, C., Marsella, A., Saracino, B., Petrongari, M., & Ferraro, A. et al. (2013). Evidence from a breast cancer hypofractionated schedule: late skin toxicity assessed by ultrasound. J Exp Clin Cancer Res, 32(1), 80.
Malkinson, F. & Keane, J. (1981). Radiobiology of the Skin: Review of Some Effects on Epidermis and Hair. Journal Of Investigative Dermatology, 77(1), 133-138.
Rocha, B., Gombar, F., Barcellos, L., Costa, W., Barcellos Sampaio, F., & Ramos, C. (2011). Glutamine supplementation prevents collagen expression damage in healthy urinary bladder caused by radiotherapy. Nutrition, 27(7-8), 809-815.
Zhou, J., Fang, L., Xie, H., Yao, W., Zhou, X., & Xiong, Z. (2015). A pilot study for observation of the efficacy of liuhedan in treating breast cancer associated radiodermatitis. Current Oncology, 22(6), 453. http://dx.doi.org/10.3747/co.22.2725