Palliative Radiotherapy: Run With the Hare and Hunt With the Hounds
Authors: Francesco Fiorica, Massimiliano Berretta
Journal: Journal of Clinical Oncology (2013)

study on palliative radiotherapy in metastatic non–small-cell lung cancer. These population-based cohort data confirm the important role of radiotherapy in palliative care; more than 50% of patients received radiotherapy. The authors concluded that a substantial proportion of patients receive more treatments and at higher doses than what is supported by current evidence. There is a continued debate over the appropriate fractionation scheme for the most effective regimen of palliative radiation therapy. Meta-analysis and randomized clinical trials suggest that single-fraction radiotherapy offers more pain relief than fractionated schedules and reduces the travel and treatment costs. 2-5 All these studies evaluated treatment effect on pain relief and duration of response, yet this assessment remains difficult and subjective. In addition, it is difficult to identify which patients need radiation as a purely palliative approach. If we focus on a median survival after metastatic diagnosis of 20 weeks, as reported in this study, 1 a long radiation treatment period (4 to 6 weeks, the standard used in a radiation therapy curative approach) is a large proportion of a patient’s remaining lifetime; that being so, it is necessary to use shorter fraction schedules with a higher dose per fraction to achieve the outcome as soon as possible. These radiation schedules result in less troublesome acute adverse effects that lead to poor quality of life. Late radiation adverse effects are not considered, because they appear after 6 months. However, here too, it is necessary to differentiate between pain relief for solid tumors pushing on nociceptors and palliative treatment for tumors occluding a small anatomic space. In the first, radiosensitive host cells—including macrophages and osteoclasts, which respond to low doses of ionizing radiation by apoptosis—may be therapeutic targets. Roentgen therapy or single-beam megavoltage radiotherapy (used in most clinical trials) obtains pain relief despite underdosing, which suggests activity on an inflammatory response pathway. In the second, palliative response seems to be related to the degree of shrinkage of the tumor, so it is not surprising if an increase in survival is demonstrated in patients with locally advanced lung cancer with higher doses of radiotherapy. If 20% of patients remain alive at 15 months, then there is a fine line between a palliative and a curative treatment. There is sufficient time to develop late adverse effects, creating a detrimental effect on quality of life, considering that hypofractionation correlates to a higher rate of late effects. Furthermore, patients treated with a single radiation fraction have greater possibility of being retreated. Observed retreatment rates were higher with the use of a single fraction at 20% to 25% compared with 7% to 12% after multifraction regimens. 3,4 In these cases, the aim of radiotherapy is to obtain an effective response and also to minimize associated long-term tissue damage. To run with the hare and hunt with the hounds, radiation oncologists have used a moderately hypofractionated (30 Gy in 10 fractions) schedule to obtain acceptable acute and late adverse effects within an appropriate timescale. Considering all this, at the present time, there are no clear objective criteria to define which patients need purely palliative radiotherapy, and this may form the basis of reluctance to adopt single fractionation as standard practice.