Radiation therapy in the management of symptomatic bone metastases: the effect of total dose and histology on pain relief and response duration

Reviewers: Kenneth Blank, MD
Source: International Journal of Radiation Oncology, Biology and Physics1998 Dec 1;42(5):1119-26

Background

When cancer is advanced, one of the most important roles of the oncologist is helping to relieve the patient's pain. Palliative care can be achieved in a variety of ways. Opioid analgesics offer a fast and very effectivemethod of pain control. However, opioids can produce severe side effects,including constipation and somnolence. Radiation therapy used inconjunction with, or as an alternative to, opioids can readily decreasecancer pain with fewer side effects.

The optimal method with which to administer palliative radiotherapy iscontroversial. A protracted course, lasting several weeks, may give longlasting pain relief, but burdens the patient with daily trips to a radiotherapy center. Small trials suggest shorter courses with larger fractions offer similar pain relief. However, a randomized trial performed by the Radiation Therapy Oncology Group (RTOG) in the early 1980s found protracted courses to offer better pain control. In order to evaluate the relative efficacy of different methods of palliative radiotherapy as well as to identify variables that may influence pain response to radiation, physicians from Italy performed a prospective analysis on patients receiving radiotherapy for bone metastases from various primary sites.

Materials and Methods

205 patients with 255 bone metastases were treated with radiotherapy at the Radiation Therapy Center in Latina, Italy. The most common primary site was breast (56% of patients), followed by non-small cell lung cancer (14%) and prostate cancer (11%). The spine was involved by metastases in half the patients.

Patients were treated with anterior and posterior fields, from using a linear accelerator producing 6MV photons. Three fractionation schedules were employed: 1] Conventional course (40-46Gy in 20-25 fractions over 5-5.5 weeks); 2] Short course (30-36Gy in 10-12 fractions in 2-2.3 weeks); 3] Fast course (8-28Gy in 1-4 fractions). The large majority of patients in the conventional, short and fast courses were treated with daily fractions of 1.8-2.0Gy, 2.5-3.0Gy and 5.0-8.0Gy, respectively. The course of radiotherapy was determined by the treating physician and based uponseveral factors including the patient's life expectancy, field size andtumor location.

Pain relief was assessed during and after treatment using a self-reportquestionnaire detailing subjective pain control and use of narcoticanalgesia. Pain intensity was graded by each patient on a scale of 0 (nopain) to 10 (severe pain). Analgesic usage was rated on a five-point scale assessing both strength and frequency (0=no opioid use, 5=strong opioids used more than once per day). In patients with more than one painful metastasis, the subjective assessment of pain relief was the only scale used as other painful sites influenced the analgesic assessment.

Complete pain relief was defined as less than three on the pain scale orzero on the narcotic scale. Partial relief was a pain rating of three orfour, or one or two on the narcotic scale. Patients were excluded if theywere greater than 85 years of age, had a life expectancy less than sixmonths or had previously received radiation to the painful site. Patientswere followed until death.

Results

Fourteen percent of patients achieved complete pain relief and 58% partial pain relief. Prostate and breast cancer metastases were more responsive than those from non-small cell lung cancer with overall (partial plus complete) pain relief occurring in 51% of patients with lung cancer and 85% and 90% of patients with breast and prostate cancer, respectively. The site of bony metastases also influenced pain relief. Overall pain relief for pelvic, spine and extremity lesions were 81%, 79% and 66%, respectively.

The duration of pain relief depended largely on whether a compete orpartial relief was obtained. Of patients with complete relief, 82%were pain free for three years compared to 43% for patients obtainingpartial relief. The conventional course (doses 40-46) yieldedsignificantly better relief than the short or fast courses. The duration of pain control was also better following a conventional course, with thethree-year pain-free rates of 85%, 76% and 32% for patients treated withconventional, short and fast courses, respectively

Univariate analysis found pain relief and long term pain control to beassociated with total dose, tumor histology, site, performance status andnumber of metastases. Multivariate analysis, using complete pain relief and time to pain progression as endpoints, demonstrated a highly significant effect of total radiation dose and performance status, with higher doses and more favorable performance status predicting better pain and longer responses.

Conclusions

This prospective study supports the Radiation Therapy Oncology Grouprandomized study in demonstrating better and more durable pain relieffollowing a protracted course of radiotherapy. In contrast, a study fromthe Royal Marsden Hospital comparing a single fraction of 8Gy to 30Gy inten fractions found no difference in pain control. However, that study iscriticized because an excess number of early deaths may have confounded the analysis of long term pain control.

The schedule of radiotherapy for painful bony metastases must beindividualized based on a number of factors including life expectancy,tumor site, field size and the ease with which the patient can travel tothe hospital. However, the results of this study and others clearlyindicate that protracted course radiotherapy produces a more complete anddurable response compared to a short course.