Comparison of Single Versus Multiple Fractions for Palliative Treatment of Painful Bone Metastasis: First Study from North West India

INTRODUCTION

Bone metastasis is a usual cause of pain in advanced cancer. With improving diagnostic and therapeutic management of cancer, the life expectancy of cancer patients is increasing; thus, there are higher chances of development of distant metastasis in the late life of these patients. Approximately 20% of cancer patients present with symptoms of bone metastasis itself.[1] The most common tumor to be associated with bone metastasis in males is cancer of the lung, followed by prostate; while in females, breast and lung cancers are the usual primary sites at our center.[2] Other common tumors to be associated with bone metastasis include kidney and thyroid. Bone metastasis can cause severe and debilitating effects, including pain, hypercalcemia, pathological fracture and spinal cord compression.[3] Radiation therapy is usually adjunct to provide palliative relief to painful bone metastasis in 50-80% of the patients, while about 35% of patients achieve complete pain relief.[4] Treatment of bone metastasis is aimed to provide pain relief, avoiding fracture and maintenance of organ function thus providing overall better quality of life to the patients.

Management of bone metastasis requires multimodality care including the efforts of a radiation oncologist, pain medicine specialist, medical oncologist and surgeon. Opioid and non-steroidal anti-inflammatory drugs (NSAIDs) may not always provide satisfactory pain relief due to inadequate analgesic response, associated adverse effects and poor patient compliance.[5] Radiation is highly effective for palliation of symptoms in such condition.[6] Hartsell et al. suggested radiotherapy to alter osteoclast-mediated bone resorption thus explaining the similar effect of pain relief with a single fraction or hypofractionated treatment.[7] There is no single regimen that is superior over the other regimen in terms of pain relief.[8] The Radiation Therapy Oncology Group (RTOG) studied various fractionation schedules and concluded that short-course treatments are as effective as longer treatments in terms of pain relief.[9] The most commonly used schedule is 30 Gy in 10 fractions delivered over 2 weeks.[10111213] This prospective study aims to analyze the pain-relieving efficacy of different radiation fractionation schedules -8 Gy administered in a single fraction and 30 Gy administered in 10 fractions.

MATERIALS AND METHODS

STATISTICAL ANALYSIS

Descriptive statistical analysis was performed for quantitative data and frequency tables were drawn for qualitative data. For qualitative variables, Chi-square was used to investigate the relationship between the two variables. Fisher's exact test was used when the assumptions of the Chi-square test were not satisfied. For all the tests, P < 0.05 was considered as the significance level. All statistical analyses were performed using SPSS software for windows version 20.0 (IBM Corp, Armonk, NY, USA).

RESULTS

Two hundred and fifty consecutive patients of bone metastasis were evaluated for the study, with 63 patients being excluded due to non-fulfillment of the inclusion criteria. The major cause of exclusion was bone metastasis other than vertebra (n = 44, 17.6%) and poor ECOG performance status (n = 15, 6%). Thus, 187 patients, of whom 64% were male, were included in this study. The median age of the patients was 57 years. The primary site was breast in 31%, lung in 33%, prostate in 17%, renal in 4% and thyroid in 3%. Seventy-one percent of the patients had metastasis only to the vertebra while the remaining had involvement of the pelvic bones as well [Table 1]. Sixty-two percent of the patients received a single fraction while the remaining received 10 fractions. In the 10-fraction group, overall response was present in 60% of the patients. Stable pain was present in 23% of the patients while 9% patients had progressive pain. At 1 month of completion of treatment, 9% patients were lost to follow-up. In the single-fraction arm, overall response was seen in 58%, stable pain in 27% and progressive pain in 7% of the patients. Six percent of the cases were lost to follow-up [Table 2 and Figure 1]. At 1 month of follow-up, pain relief in the single-fraction arm was slightly inferior to the 10-fractions arm (P = 0.09). There were no differences in the response on the basis of site of metastases, sociodemographic parameters and the general condition of the patients.

Table 1 Characteristics of patients at the time of selection for the study

Table 2 Response to radiation in terms of pain relief at 30 days of completion of treatment

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Figure 1

Line diagram showing the percentage of patients with overall response (pain relief) after radiotherapy according to the fractionation schedule used

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DISCUSSION

The management of bone metastasis should be aimed at providing maximum relief of pain with minimum morbidity in the shortest possible hospital admission time.[1415] Conventional schedules require longer hospital stay and thus are unsuitable for patients with poor general condition. We evaluated the perspective of using a single high-dose (8 Gy) fraction in palliation of pain of bony metastasis versus 10 fractions of 3 Gy. The radiation treatment was given in addition to the analgesics to relieve pain and other distressing symptoms. Long-term use of potent analgesics such as NSAIDS could cause gastrointestinal side-effects and nephrotoxicity, which may further reduce the quality of life.[5] Thus, appropriate schedule of the radiotherapy may prove a blessing in disguise in improving the quality of life with minimum toxicity and morbidity. In our study, the most common site of primary tumor was the lung, followed by the prostate, while there were a few from the thyroid and kidney as well. The RTOG studied various fractionation schedules for pain-relieving radiotherapy and found equivalent results between hypofractionated radiation and longer fractionated schedules.[1617]

In 2009, the RTOG 97-14 published data of 898 patients with painful bony metastasis having primaries of breast and prostate cancer. The patients were randomly allocated in two arms, receiving doses similar to our study. The result of pain relief was similar, with a slightly greater need for retreatment for the single-fraction arm.[18]

We found equivalent results between the single-fraction arm and the 10-fractions arm. Immediate pain relief was slightly better in the single high-dose arm.[9192021] However, at 1 month of follow-up, pain relief in the single-fraction arm was slightly inferior, although statistically non-significant, than the 10-fractions arm. Because the follow-up of the patients was limited in our study, the need of retreatment cannot be definitely commented upon. However, in the RTOG trial with a larger follow-up period, higher need of retreatment was required in the single-fraction arm.

Coli et al. reported an 8% retreatment rate to same anatomic site due to recurrent pain with fractionated treatment versus 20% retreatment after single fraction.[22] Single-fraction treatment is optimal as it improves the therapeutic convenience of patient, patients’ family and caregiver. The incidence of temporary flare of bone pain may be slightly higher with single-fraction treatment. Thus, concurrent use of anti-inflammatory drugs is indicated to minimize flare symptoms.[23] A higher single-dose fraction is usually preferred in patients with spinal cord compression or radical nerve pain.²⁴ The American task force found that there were no long-term side-effects from the single 8 Gy fraction that may limit its use for patients with painful bony metastasis.

CONCLUSIONS

The authors would like to conclude that single-fraction treatment for bony metastasis is as effective as multiple fractions to relieve bony pain and provides treatment convenience to both the patient and the caregiver.