Radiation Dermatitis Evidence From a Clinical Practice Guideline

  Patients undergoing external radiation therapy to treat cancer or prevent its recurrence often experience acute radiation dermatitis (RD) beginning within 2-3 weeks after the start of radiation therapy, or “late” RD lasting more than 90 days. Acute RD ranges from mild erythema to moist or dry desquamation or ulceration, depending on radiation dose per fraction or total dose; location, structure, and volume of treated tissue or its prior or concomitant treatments; or patient age, genetic factors, and skin condition.^1,2 Late RD progresses to telangectasia or fibrosis. These wounds can be so severe that they become an ordeal for the patient, reducing quality of life or capacity to continue potentially life-saving radiation therapy.

  This month’s Evidence Corner reviews the state of the art of evidence-based RD management as reflected in one RCT,¹ and RCT evidence from a systematic review supporting a clinical practice guideline to prevent and treat RD.² After years of focusing on cancer cells, clinical research is laying the foundation for improving patient-oriented outcomes associated with the side effects of radiation therapy.

  Laura Bolton, PhD
Adjunct Associate Professor
Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ

  Reference: Wong RK, Bensadoun RJ, Boers-Doets CB, et al. Clinical practice guidelines for the prevention and treatment of acute and late radiation reactions from the MASCC Skin Toxicity Study Group. Support Care Cancer. 2013;21(10):2933-2948.

  Rationale: Clinical practice to prevent and manage radiation dermatitis (RD) varies widely due to the lack of high quality randomized controlled trials (RCTs) supporting specific interventions addressing early RD, and a total absence of RCTs on managing late RD. An evidence-based interdisciplinary guideline would increase consistency of care, potentially improving clinical outcomes.

  Objective: Develop evidence-based recommendations for use by general practitioners, dermatologists, radiation oncologists, medical oncologists, surgical oncologists, oncology nurses, oncology pharmacists, and radiation therapists for prevention and treatment of acute RD and the treatment of established late RD.

  Methods: A group of international, interdisciplinary experts in dermatology, medical and supportive oncology, health-related quality-of-life, and pharmaco-vigilance searched MEDLINE, Cochrane, and CancerLit reference databases from 1980 to 2011 for MESH terms relevant to controlled studies or reviews or meta-analyses of same, reporting early or late standardized RD outcome severity measures. The primary outcome was incidence of RD > 2 (moist desquamation with moderate erythema and/or edema) on the validated Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE) scale. Other outcomes included were pain, itching, or quality of life when available. Strength of evidence was highest—level I—if supported by meta-analysis or RCTs with high power; level II if supported by RCTs with low power; level III if supported by non-randomized controlled or case-controlled studies; level IV if supported by descriptive or case studies; or level V if supported by case reports and clinical examples. Strength of Recommendation ranged from highest—level A—if supported by level I or consistent level II evidence to lowest—level D—indicating little or no evidence.

  Results: Fifty-six studies met the inclusion criteria for supporting guideline recommended interventions to prevent or treat RD. Of these, 45 RCTs addressed prevention of acute RD and 9 addressed treatment, including 1 trial that explored sequential effects of preventing and treating acute RD. One RCT and 1 prospective observational study explored interventions to manage late RD telangiectasia, and 2 single-arm studies explored late RD fibrosis. Multiple RCTs supported recommendations to allow patients to wash the affected skin with water and optional mild soap or shampoo, and to use antiperspirants. Some anti-inflammatory or moisturizing formulations had weak evidence for preventing RD, but most interventions to prevent, treat, or heal RD were based on insufficient evidence to support or refute their use (Table 1).

  Authors’ Conclusion: More rigorous RCTs are required to support clinical practice decisions to prevent or treat RD.

  Reference: Di Franco R, Sammarco E, Calvanese MG, et al. Preventing the acute skin side effects in patients treated with radiotherapy for breast cancer: the use of corneometry in order to evaluate the protective effect of moisturizing creams. Radiat Oncol. 201312;8:57-64.

  Rationale: Preventing or treating RD are high priorities for managing outcomes for patients with breast cancer. Effects of topical therapy to prevent RD are typically measured subjectively.

  Objective: Evaluate an instrumental measurement of assessing the skin damage induced by radiation therapy.

  Methods: Between January and December 2011, an Italian multidisciplinary ambulatory radiation clinic randomly assigned 100 female patients with breast cancer, 29-75 years of age, who were candidates for radiation therapy to receive 1 of 5 marketed skin moisturizing creams to prevent RD: 1) betaglucan sodium hyaluronate, 2) a vitis vinifera A combination, 3) an aloe vera alginate combination, 4) a phytosterol formula, or 5) a thermal water formulation. All subjects were free of lymph node involvement after conservative surgical excision to a cancer-free margin. They began applying their assigned topical cream to the irradiated skin 2-3 times daily 15 days before radiation therapy began, and continued treatment 1 month after the end of radiation therapy. They used oil-based soap, wore loose-fitting cotton clothing, and avoided treating the skin within 3 hours before radiation therapy, which consisted of 6 MV photons, with a whole-breast tangential field dose of 50 Gy (2 Gy/fraction), and a subsequent additional dose to the tumor bed of 10 Gy (2 Gy/fraction). Three-dimensional target tissue volume doses were set in International Commission on Radiation Units using the radiation oncology treatment planning system (Pinnacle Treatment Planning System, Phillips, Andover, MA) after a CT-scan simulation 2 weeks before the first radiation therapy. No other creams or perfumes were applied to the affected skin during the study. Baseline skin hydration and Fitzpatrick phototype classification³ were recorded. Patients’ radiated skin hydration was measured as skin dielectric constant units using a scientific device (Corneometer CM 820, CK Electronic, Cologne, Germany) and evaluated jointly by the dermatologist and clinical radiologist using the RTOG scale⁴ for RD, once before treatment began, weekly during radiotherapy, and 1 month after the last radiation treatment.

  Results: All 20 subjects in each of the 5 groups completed radiotherapy with no statistically significant treatment group differences reported in corneometry or clinical evaluations. No Grade 4 RD (ie, ulcerations/hemorrhage/necrosis) was observed in any subject, and only 5 subjects, who were treated with the phytosterol, experienced Grade 3 RD (ie, desquamation with widespread sweating and marked edema). Corneometry remained within the normal range of 30-90 units for all measurements, rising from means near 40 units (range 30.9-44.6) at baseline to about 70 units (range 37.2-77.0) at the end of radiotherapy. There were no significant correlations between subject variables or systemic therapies and measurements of RD, resulting in no significant differences in relative risk, absolute risk reduction or odds ratios of RD for any variable studied.

  Authors’ Conclusions: Good skin hydration of the affected area before, during, and after radiotherapy can improve skin tolerance to treatment and acute RD outcomes. The lack of significant effects on RD severity for subject, systemic, or topical therapy was likely due to the small sample sizes studied.

  Clinical Perspective: Results reported by Di Franco et al¹ appear to confirm the importance of maintaining skin hydration during radiation therapy. This conclusion would have been more compelling if the moisturizing therapies had been compared with a non-moisturizing standard of care. The results reported do not clearly demonstrate that corneometry can distinguish between effective and ineffective acute RD prophylaxis interventions because all those studied moisturized radiation-treated skin sufficiently to prevent the worst grades of acute RD. Differences among RD prophylactic efficacy were too subtle to be statistically significant with such small samples. Supporting RCTs were mainly on patients with breast cancer. More research is needed on preventing side effects important to patients at other radiated sites, and maintaining functionality of deeper levels of tissue damage, such as urinary tract function. Improving knowledge about these side effects and ways to prevent them can bring radiation therapy into a golden age of clinician- and patient-informed radiation therapy choices that optimize both quality of life and clinical outcomes.