Cost effectiveness is another major
Cost effectiveness is another major concern for the governments in countries with public health system. Van-den Hout WB et al. at Netherlands  did a cost utility analysis showing the cost of radiation treatment including re-treatment for bone metastases using SF versus MF were €2438 versus €3311 respectively. RTOG 9714 groups showed the expected mean cost was US $1009 and US $2322 for treating with 8Gy/1Fr and 30Gy/10Fr respectively . It is evident that SF is more cost effective than MF treatment. Physicians are therefore advised to consider more single fractioned radiotherapy on uncomplicated bone metastases based on the similar efficacy and cost effectiveness. Even taking into account of higher re-treatment rate using initial SF radiotherapy, the cost is still lower than performing initial SF and retreatment with MF radiotherapy .
In palliative medicine, maintaining the quality of life (QOL) is the most important goal of both patients and palliative physicians. However, there is no trial addressing the QOL of patient receiving re-irradiation for their painful bone metastases. The development of EORTC-QLQ BM22  would probably standardize the outcomes on QOL in upcoming trials, and hopefully, we will have a better idea on how re-irradiation improves the QOL of patients in quantitative means. A simplified treatment plan would definitely help in improving the QOL of patient. Successful re-irradiation to painful bony sites may potentially minimize the use of analgesics. Thus, patients would definitely benefit in terms of improving their QOL.
Re-irradiation of other organs Re-irradiation of other body sites is increasingly attempted by physicians worldwide. However, randomized control trials are again lacking. The response rate of re-irradiating each site varies. Table 1 shows a comparison of response rate of re-irradiating different organs. Late toxicities are challenging for physicians. Tissue tolerance of various organs had been discussed by Nieder et al.  in 2000. Having said that toxicities were observed after exceeding a certain cumulative dose at BED at 2Gy, oncologists often try their best to stretch the maximal tolerance of major organs by using better dose painting technique to minimize dose to organs at risk, and at the same time giving the best local control with irradiation. Dose constraints of the Ellagic acid stem and brain tolerance in re-treatment of head and neck cancer recurrences were well documented on RTOG 9610 and 9911 protocols, though long term results of complications are awaited. Comparing re-irradiating organs with painful bone metastases especially non-axial bones, there is much less concern for late complications of bones.
Alternatives in treating bone pain recurrence Huisman et al.  suggested physicians to explore more on other sorts of treatment including radionuclides and bone targeting therapy. It is therefore worthwhile to understand more on the response rate and cost effective of other alternatives in comparison with that of re-irradiation of bone metastases.
Re-irradiation of bone metastases is efficacious
Who, when and how to re-irradiate recurrent painful bone metastases ‘Who’ would likely respond to re-treatment? Jeremic et al.  conducted a prospective trial with 4 Gy in one fraction after initial 4 Gy single fraction treatment with a response rate of 74%. Those who initially had a complete response were more likely to achieve another complete response then those with partial response (p=0.042), and those with initial partial response were also more likely to achieve another partial response (p=0.00054). Even for non-responders, 46% did have a partial or complete response with re-irradiation. Jeremic et al.  later conducted another study on 25 patients who receive 4Gy in one fraction after given single fraction radiotherapy (4, 6, or 8 Gy plus 4 Gy) for twice, suggested a response rate of 84%, and 67% in previous responders and non –responders respectively. It seems that both initial responders and non- responders would benefit from re-irradiation for one or more times. Van den Linden et al.  reported that the pain score before retreatment significantly predicted retreatment (P<0.001). Retreatment for non-responders was successful in 66% SF vs. 33% MF patients (p=0.13), and retreatment for progression was successful in 70% SF vs. 57% MF patients (p=0.24). However, with the background that SF is as effective as MF treatment in terms of pain response , SF is encouraged to be implemented as first line treatment in uncomplicated bone metastases, thus higher response rate of re-treatment may be anticipated in subsequent trials. Overall, it seems that no matter SF or MF treatment was initially given and whether patients responded initially, those presented with recurrence of bone pain would definitely worth being considered for re-irradiation. Those who responded initially may benefit more.