Our modeling of uncomplicated TCP is significant, in our view, as it demonstrates the capacity of radiotherapy to sterilize or cure small HCC tumors with a relatively high probability. Radiotherapy has only rarely been considered as a curative treatment modality. Our findings are supported by recent clinical reports

which have demonstrated impressive complete radiological response rates (ranging 80–87.5%) for small HCC,28,29 although this end-point is not a reliable indicator of sterilization. While the potential for radiotherapy to cure smaller HCC exists, it is also clear from our modeling that large tumors are unlikely to be sterilized. Despite this, radiotherapy to large tumors will result in a large proportion CH5424802 concentration of clonogens being killed. This can be clinically useful in terms of tumor shrinkage or delay MK-2206 clinical trial of growth or recurrence. The clinical benefits of radiotherapy in the setting of large, incurable HCC have been widely reported in non-randomized clinical trials and recently reviewed by Hawkins et al.27 In general, radiotherapy, usually combined with transarterial chemoembolization (TACE), has been associated with partial (>50%) radiological responses in over 50% of patients and complete disappearance

of tumor thrombus in major veins has been reported in more than 30% of cases.30,31 The tumor control probability modeling also highlights the need for high radiation doses to sterilize HCC following other local therapy of HCC which may see more leave residual subclinical disease. This is an important consideration when radiotherapy is required to provide adjuvant therapy following initial treatment with other modalities such as TACE or radiofrequency ablation

(RFA). There are several important advantages of standard external beam radiotherapy techniques which warrant further discussion. First, radiotherapy is an established cancer therapy which is already widely accessible and the techniques required are routinely available. This differs from other therapies (liver transplantation and resection, RFA and TACE) which may be less accessible and the results more operator-dependent. We believe that current CT planning techniques combined with standard treatment are sufficient for most cases, although achieving greater accuracy, which is desirable for small tumors, may be possible using intensity modulation or stereotactic techniques if available. Even so, inaccuracies due to movement must be recognized. In HCC endemic areas of the developing world, 90Y microspheres are not generally available and heavy ion techniques are prohibitively expensive. An advantage of radiotherapy over chemotherapy is greater tumor cell kill. For typical cancers, radiotherapy may achieve approximately 10–12 or more log kill, compared with approximately up to 6 log kill associated with chemotherapy.