Using the previously reported keywords in Scopus, PubMed, Embase, and Cochrane Library, a total of 133 articles were obtained. Among these articles, 70 were excluded entirely because of duplication and eight were excluded for other reasons (e.g., comments, response letters to the editor). Furthermore, 37 records were excluded because the title and abstract did not match the inclusion criteria, and the full texts of the remaining 18 studies were assessed; one study was not accessible. Among the 17 papers, two were secondary analysis of clinical trials and one study was incomplete, resulting in the unavailability of complete results. Thus, 14 papers were ultimately selected for scoping review because they fulfilled the set inclusion criteria. Figure 2 depicts the search strategy utilized for the review report according to the PRISMA guidelines.

Search strategy employed according to the PRISMA flowchart

NCI National Cancer Institute, RTOG Radiation Therapy Oncology Group, CTCAE Common Terminology Criteria for Adverse Events, RISRAS Radiotherapy-Induced Skin Reaction Assessment Scale.

The pathobiology of RD includes direct tissue damage and the recruitment of inflammatory cells in response to skin irradiation which in turn damages epidermal and endothelial cells. Furthermore, free radicals released due to radiation induced DNA damage, along with inflammatory cytokines, can cause ulceration and other clinical abnormalities such as erythema. The intensity of skin reactions is influenced by a number of radiation parameters, including the overall treatment period, dose per fraction, type and energy of the beam, and total amount of radiation exposed to the skin [46].

Table 4 summarizes the outcomes of the studies related to the applicability of PBMT in treating RD. The 14 studies considered were of different study types, analyzing the effect of PBMT mainly on breast cancer (BC), head and neck cancer (HNC), and other cancer types, such as cervical and anal cancer. The study types included randomized controlled trials (35.71%), case reports (21.42%), prospective studies (14.28%), single institution analysis (14.28%), pilot studies (7.14%), and case series (7.14%). The influence of PBMT has been extensively studied in BC followed by HNC. RTOG and CTCAE are the commonly used scale to assess treatment efficacy of PBMT.

Among the 14 research investigations analyzed, with the exception of two studies, [32, 37] the remaining studies demonstrated favorable results regarding the efficacy of PBMT in the treatment of radiation-induced dermatitis in individuals diagnosed with cancer. In studies with positive outcomes, the PBMT has been observed to be beneficial in reducing the severity of the RD. PBMT application has been studied as a preventive measure for the development of RD (35.71%), for the treatment and management of RD severity (50%), and for both the prevention and cure of RD (14.29%).

The Censabella and Robijns groups have extensively studied PBMT (808 and 905 nm) based management of RD in breast cancer. They began their research with pilot study (DERMIS trial) [33], whose results provided sufficient positive outcomes to conduct the TRANSDERMIS trial, which had a larger sample size and provided a definitive beneficial effect of PBMT in treating RD [35]. A retrospective study of the TRANSDERMIS trial patient population was conducted which ensured the long-term safety of the technique with no locoregional recurrence or new tumor formation [38]. Furthermore, the applicability of PBMT on patients undergoing hypofractioned whole-breast irradiation was not significant based on the basis of the LABRA trial results [37]. The DERMISHEAD trial focused on managing the RD developed in head and neck patients, and the results supported the implementation of PBMT among cancer patients [40].

Table 5 summarizes the PBMT parameters used in the studies. The light sources used in the reported studies included LEDs (35.7%) and diode lasers (57.14%), with wavelengths ranging from red to near infrared light, i.e., wavelengths from 590 to 905 nm. The PBMT treatment included either a single laser wavelength (35.71%) or a combination of wavelengths (64.29%). The reported laser mode ranges from pulsed mode (21.42%), continuous mode (42.85%), and continuous pulsed wave mode (28.57%). Compared with classical laser therapy, multi-wave locked system (MLS) laser therapy emits lasers in continuous pulsed wave mode, which is considered to be more beneficial, as continuous lasers used to reduce inflammation whereas pulsed lasers used to induce analgesic effects [36]. Furthermore, irradiances range from 44.6 to 168 mW/cm2 and fluences ranging from 3 to 67 J/cm2 have been reported. Depending on the scanner, a contact or noncontact application method was used. Notably, the study by Zhang et al. fails to mention the complete details of the PBMT parameters [27], whereas other studies lacked specific details of power, fluence, and beam area. The power mentioned in the studies are variable as some have given the peak power alone, while others have average power. Thus, it is necessary to provide complete details of the PBMT parameters for comparison of the studies and to understand the efficiency of treatment.

In addition to the effects of PBMT on the severity of RD, other important parameters, such as pain level, RT interruption, and QoL have also been reported. Approximately six studies have evaluated pain levels via the visual analog scale (VAS), or the NCI-5 point scale for grading skin reaction questionnaire and the numerical rating scale. Among them, two studies were performed on breast cancer patients; study by Strouthos et al. reported that 60% of the treatment group reported no pain, whereas in the control group only 28.9% reported no pain with the rest reporting pain intensity up to VAS-5 scale [34]. In contrast, the study by Fife et al. revealed no difference in pain level after PBMT treatment [32]. Zhang et al. reported pain reduction in the HNC patients’ treatment group, whereas increased pain was observed in the control group after each RT [27]. A study by Bensadoun et al. investigated pain intensity in both BC and HNC patients and observed significant pain reduction as 87.5% reported no pain [47]. Two case studies on anal cancer patients also reported reduction in pain intensity over the course of treatment [43, 45]. On the basis of these studies, we have greater confidence in the application of PBMT as an analgesic in the treatment and management of RD.

Interruption of the RT treatment plan due to severe skin reactions is considered another major setback. Among the reported studies, four reported RT interruption. Deland et al. reported that 5.3% of patients in the treatment group and 67.9% of those in the control group experienced RT interruption [31]. Fife et al. reported that 11.1% and 6.7% of sample population discontinued RT from the treatment and control groups respectively [32]. Strouthos et al. reported no RT interruption in the treatment group, but 4.4% of the control participants discontinued the treatment [34]. Aires et al. reported that 1% of samples discontinued RT due to RD [41]. Furthermore, a patient’s quality of life (QoL) during treatment plays a very important role in patient satisfaction and continuation of treatment. Three studies evaluated the QoL of patients on the basis of the skindex-16. Based on these findings, only one study reported improvement in QoL [35], whereas the other two studies reported no significant improvement in the PBMT group [33, 40].

There has been a debate about the possible tumor promoting effect of PBMT due to residual cancerous cells. An in vivo study investigating the PBMT effect on melanoma reported induction of tumor growth leading to angiogenesis [48]. However, another study reported PBMT to be safe for amelanotic non-pigmented melanoma, whereas for melanotic pigmented cells the PBMT triggers different responses depending on the light parameters, i.e., NIR laser at lower dose was observed to be promoting the cell invasiveness, whereas red light reduced the cell invasiveness [49]. Further, potential interference of PBMT in the anti-cancer treatment plan has also been one of the concerns. Recent study involving orthotopic animal model bearing tumor has further investigated these claims, wherein PBMT followed by radiation therapy did not reduce the efficiency of the RT in killing tumor cells [50]. The PBMT-related risk assessed in the studies reported no adverse effects either on RD severity or the cancer reoccurrence during the course of the study. [32, 37] Even among the two studies with no significant outcome, the one that presented no adverse effects rather failed to present meaningful outcomes compared to the control group [32, 37]. Long-term follow-up (5 years after end of RT) was conducted for the TRANSDERMIS study population. The study reported no significant variation in disease free survival (73.7% vs. 98.3%), cancer free survival (68.4% vs. 77.8%), and overall survival (87.9% vs. 98.3%) between control and treatment group, thus, suggesting that the PBMT treatment did not elicit tumor recurrence over an extended period of time [38]. However, this is the only study that has conducted long-term follow-up, so more studies on long-term effects on cancer reoccurrence and tumor development are needed to confirm the safety of PBMT.

The skincare regime plays a major role in managing skin reactions and maintaining the skin barrier after undergoing RT, thereby reducing the severity of RD. During RT, the common skin issues include erythema, dryness, and hyperpigmentation. A secondary analysis of the TRANSDERMIS study population has revealed that the biophysical skin measurements were mainly moist desquamation which was significantly reduced in the treatment group that underwent PBMT. In addition, large breast volume has been reported to be a risk factor for the development of moist desquamation [34]. In addition to the benefits from PBMT, most studies have suggested the institutional skincare protocols for patients, with the focus on maintaining the cleanliness of the area along with the regular application of topical agents to counter irritation. The commonly recommended topical agents in this area include Aquaphor, a petroleum-based emollient [31, 32], Flamigel®, a hydroactive colloid, Mepilex®, a silicone dressing [33, 35,36,37, 40], Palmitoylethanolamide cream, phenol-methanal-urea-polycondensate cream [34], and 1% silver sulfadiazine, an antibiotic and betamethasone valerate, a steroid agent [44]. Among these agents, few have been proven to be effective individually in the management of RD. Flamigel® has been shown to be beneficial in reducing pain and soothing effects; however, no effect on erythema has been reported [51]. Similarly, silver sulfadiazine and betamethasone valerate have also been shown to reduce the severity of RD [52, 53], and Mepilex Lite dressings are known to accelerate wound healing in RD patients [54]. Thus, the PBMT results of the studies that have included these agents in the skincare protocol could be the cumulative effect of PBMT and the topical agent rather than PBMT alone. These findings provide us with the possibility of enhancing the PBMT effect with topical agents that have been proven to be effective in treating RD such as timolol and Biafne® [55, 56].

The varied results obtained from these clinical studies can be explained only by a better understanding of the mechanism of action of PBMT on RD. Park et al. used a mouse model to evaluate the effect of PBMT (633 nm, 830 nm) on RD and reported that PBMT was able to reduce the severity of RD by reducing inflammation and dermal damage, but no significant difference was observed between the beneficial effects of 633 nm and 830 nm [57]. Another study on a rat model using an LED-based PBM apparatus for RD observed the best results in the treatment group with a combination of 630 nm + 850 nm wavelengths, as well as in the group receiving 630 nm alone, based on macroscopic evaluation, i.e., RTOG grading of the wound site by investigators. Further confirmation done via gene expression analysis revealed that both tumor necrosis factor (TNF-α) and interleukin-10 levels were lower than those in the control group [58]. In radiation induced skin reaction, the NF-Kb pathway is activated along with the production of many pro-inflammatory cytokines such as cyclooxygenase (COX), TNF-α, and chemokines; thus, inhibition of these can improve skin tolerance to RT [59]. It is possible that the impact of PBMT on RD follows a similar mechanism as previous studies have reported that PBMT has an anti-inflammatory effect through the inhibition of prostaglandin E2 (PGE2), COX-2, and TNF- α [58, 60].

There has also been the development of efficient PBMT devices that could make this treatment option more reliable and effective for clinical use. CareMin650 is one such device that uses LED emission (650 nm) on the surface in contact with either a derma pad or an oral pad on the basis of the site of adverse reaction mode and has reported promising results in treating RD in both HNC and BC patients. Thus, further standardization of PBMT parameters could be easily implemented in the treatment population [47]. Considering the success of these PBMT treatments in HNC and BC, this approach has also been applied in treating RD in other cancers. A case report on PBMT for lesions due to radiation therapy targeting anal canal treatment reported a reduction in the RD grade along with associated symptoms such as pain and burning sensations [45]. In another study that focused on two patients with acute cervical RD, a reduction in RD grade after RT with enhanced healing was reported [44].