A reply to ‘Efficacy and safety of widefield radiation therapy for extensive skin field cancerization remains unproven’

Abstract

We read with interest the letter to the editor by Daly et al.¹ in response to the 24-month National Dermatology Radiation Oncology Registry (NDROR; ACTRN12618000627257) publication,² which reiterates the important considerations relating to the use of widefield radiation therapy (RT), such as Volumetric Modulated Arc Therapy (VMAT) to treat extensive skin field cancerisation (SFC) in patients with current or previous invasive in-field keratinocyte cancer (KC). The NDROR is a multidisciplinary collaboration between dermatologists, radiation oncologists, nurses, and other skin cancer specialists with the aim of collecting efficacy, cosmesis, toxicity, and QoL data for skin cancer patients receiving widefield RT. It is the largest prospective cohort of its kind, necessitating publication of analyses as available.

It is important to note that extensive SFC can produce KCs causing significant morbidity and mortality, whilst field-directed therapies have poor durability—particularly for severe disease.³ A history of KCs, as well as actinic keratoses number, thickness, and prior treatment failure, all correlate with risk of new disease.^4-7 Extensive SFC should therefore be treated appropriately in line with the patient's disease presentation and treatment history. With the increasing KC incidence and the advent of new treatments, a multidisciplinary approach is required now more so than ever before. The range of specialists involved in this study, including patient assessment, is a testament to this new paradigm.

With respect to patient selection, 82% had received prior, sometimes multiple, interventions before consideration of widefield RT. Furthermore, >70% of patients had at least one co-morbidity, including surgical cautions. This confluence of factors was considered when determining appropriateness for widefield RT. We also agree that the concerns of widefield RT risks should not be diminished, which is why toxicity assessment has been a major focus of our data collections. Although longer follow-up is required, regular reporting is essential in the absence of any other contributions to the literature. This too is relevant for durability of clinical response. While we agree that the registry design precludes head-to-head comparisons with standard of care, the 10% new lesion rate reported in our study must be considered in the context of disease severity. Patients who fail prior treatment, and/or those with a history of multiple KCs have very high new lesion rates of 35%–90% within 2–4 years of treatment.^4-7

Daly et al. rightly assert that ‘selected patients with a high burden of invasive and in situ disease who are exhausting efforts to treat invasive lesions may benefit from widefield RT, but the uncertain outcome, and the long-term effects, including the potential to undermine treatment of subsequent cancers should be considered’, comporting with conclusions from our article. In line with this, we have previously recommended that VMAT for ESFC should be prescribed only by experienced radiation oncologists with access to rigorous accreditation, MDT with chart round discussion, and robust radiation-specialists nursing support.⁸

We welcome opportunities to expand research into the efficacy and safety of this intervention for extensive SFC collaborating in the design and execution of well-controlled trials with blinded outcome assessment.

L. Spelman, D. Christie, B. Wong, C. Baker, S. Shumack, R. Sinclair, C. C. Allison, P. Foley, S. Hacker, wrote and revised manuscript for intellectual content. L. Spelman, D. Christie, B. Wong, C. Baker, S. Shumack, R. Sinclair, A. E. Potter, P. Foley, S. Hacker, C. C. Allison approved the final version of the article.

The original study referred to in this letter was supported by GenesisCare Pty Ltd. The authors were responsible for all content, interpretation of the data and the decision to publish the results; they received no honoraria related to the development of this manuscript.

All authors have completed the ICMJE uniform disclosure form and declare: A. E. Potter, D. Christie, and B. Wong are employees of GenesisCare. P. Foley and C. C. Allison report no conflicts of interest in relation to GenesisCare. S. Shumack, R. Sinclair, S. Hacker, L. Spelman, C. Baker report receipt of personal fees for consultancy work from GenesisCare outside of the submitted work. L. Spelman reports being a paid advisor for the NDROR. L. Spelman, S. Shumack and C. Baker report being unpaid members of advisory panel that consults on NDROR guidelines.

Not applicable.