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The topic is related to the ONTRAC trial, which was a study conducted for the use of oral nicotinamide to reduce the risk of actinic cancers.
Actinic keratosis (AK) is formed by the proliferation of keratinocytes with varying degrees of dysplasia within the epidermis. It has the potential for malignant transformation into non-melanoma skin cancers, notably squamous cell carcinoma.
AKs usually present as an erythematous scale plaque or, or papules, which can invariably present with an irregular border. They are asymptomatic in most instances. The obvious risks of invasion into the dermis are wider metastasis of these cells, and ultimately what constitute the real risk of a squamous cell carcinoma forming out of an AK. This has led to a widespread conclusion that all AKs should be treated.
Field cancerisation is an important concept. For an AK to have developed from ultraviolet ray exposure, an entire area is equally likely to have been affected by this exposure, implying that there may be multiple keratinocytes throughout that region, which might show early dysplastic change. So, field cancerisation implies that it's not just one single area that needs to be considered, it's the entire sun-exposed area.
So when we have a patient who presents with AK, it's important to understand that we might treat the focal area purely because that lesion has converted into a recognisable AK. But if we were to leave the rest of the area, it's understandable that we might see a very high recurrence rate of new lesions which pop up in the future.
If you have had a patient who is successfully treated, it's imperative that they have frequent and detailed review of their skin, notably in the sun-exposed areas for the new occurrence of these lesions.
Sunscreen is probably the most useful modality in the prevention of AKs and subsequent skin cancers. If you look at the laboratory SPF on the tube and you compare that to the real-life SPF that a patient may enjoy by using the product data shows us that patients typically only get about half of the rating on the tube, purely because they don't apply enough, they don't reapply, they sweat it off. This leads us to the question – is sunscreen alone enough?
The takeaway is that current offerings to consumers are probably not sufficient, and there is definitely impetus of more and more universities, notably in Australia, to look at alternative or adjunctive ways to add to the prevention protocols for these patients. As consequence of the phase three on track trial, oral nicotinamide has been looked at far closer, mainly because it is a very inexpensive treatment. It also has virtually no side effect profile. It can be used by virtually any patient, and yet through the phase 3 results show significant improvement in the risk of developing future AKs and even non-melanoma skin cancer. Nicotinamide significantly enhances DNA repair and prevents the intensive immune suppression in skin. It is an anti-inflammatory as a well as an ability to significantly increase cellular energy levels. This all from the same compound that can be taken very safely at this dose presents a very compelling argument. Combined therapies with oral nicotinamide may be a very useful adjunct to further reduce the risk in these patients.