Clinical Topics & News

Palliative Radiotherapy for the Management of Metastatic Cancer

Life expectancy and tumor characteristics should be considered when making treatment recommendations for palliative radiotherapy, which can be cost-effective and provide symptom relief.

Fed Pract. 2015 May;32(suppl 4):12S-16S

Author(s):

Ruchika Gutt, MD

George Dawson, MD

Alice V. Cheuk, MD

Helen Fosmire, MD

Drew Moghanaki, MD

Maria Kelly, MD

Shruti Jolly, MD

on behalf of the VHA National Palliative Radiotherapy Taskforce

References

1. Porter A and David M. Palliative care for bone, spinal cord, brain, and liver metastases. In: Gunderson LL, Tepper JE, eds. Clinical Radiation Oncology. 2nd ed. Philadelphia, PA: Elsevier Churchill Livingstone; 2007:437-451.

2. Yamaguchi S, Ohguri T, Matsuki Y, et al. Palliative radiotherapy in patients with a poor performance status: the palliative effect is correlated with prolongation of survival time. Radiat Oncol. 2013;8:166.

3. Mac Manus MP, Matthews JP, Wada M, Wirth A, Worotniuk V, Ball DL. Unexpected long-term survival after low-dose palliative radiotherapy for non-small cell lung cancer. Cancer. 2006;106(5):1110-1116.

4. Rastogi M, Revannasiddaiah S, Gupta MK, Seam RK, Thakur P, Gupta M. When palliative treatment achieves more than palliation: instances of long-term survival after palliative radiotherapy. Indian J Palliat Care. 2012;18(2):117-121.

5. Nieder C, Pawinski A, Haukland E, Dokmo R, Phillipi I, Dalhaug A. Estimating need for palliative external beam radiotherapy in adult cancer patients. Int J Radiat Oncol Biol Phys. 2010;76(1):207-211.

6. Hoegler D. Radiotherapy for palliation of symptoms in incurable cancer. Curr Probl Cancer. 1997;21(3):129-183.

7. Expósito J, Jaén J, Alonso E, Tovar I. Use of palliative radiotherapy in brain and bone metastases (VARA II study). Radiat Oncol. 2012;7:131.

8. Konski A. Radiotherapy is a cost-effective palliative treatment for patients with bone metastasis from prostate cancer. Int J Radiat Oncol Biol Phys. 2004;60(5):1373-1378.

9. Popovic M, den Hartogh M, Zhang L, et al. Review of international patterns of practice for the treatment of painful bone metastases with palliative radiotherapy from 1993 to 2013. Radiother Oncol. 2014;111(1):11-17.

10. Lutz S, Berk L, Chang E, et al; American Society for Radiation Oncology (ASTRO). Palliative radiotherapy for bone metastases: an ASTRO evidence-based guideline. Int J Radiat Oncol Biol Phys. 2011;79(4):965-976.

11. Chow E, Harris K, Fan G, Tsao M, Sze WM. Palliative radiotherapy trials for bone metastases: a systemic review. J Clin Oncol. 2007;25(11):1423-1436.

12. Sze WM, Shelley M, Held I, Mason M. Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy—a systemic review of the randomized trials. Cochrane Database Syst Rev. 2004;(2):CD004721.

13. Steenland E, Leer JW, van Houwelingen H, et al. The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study. Radiother Oncol. 1999;52(2):101-109.

14. Krishnan MS, Epstein-Peterson Z, Chen YH, et al. Predicting life expectance in patients with metastatic cancer receiving palliative radiotherapy: the TEACHH model. Cancer. 2014;120(1):134-141.

15. Guadagnolo BA, Liao KP, Elting L, Giordano S, Buccholz TA, Shih YC. Use of radiation therapy in the last 30 days of life among a large population-based cohort of elderly patients in the United States. J Clin Oncol. 2013;31(1):80-87.

16. Moghanaki D, Cheuk AV, Fosmire H, et al; U.S. Veterans Healthcare Administration National Palliative Radiotherapy Taskforce. Availability of single fraction palliative radiotherapy for cancer patients receiving end-of-life care within the Veterans Healthcare Administration. J Palliat Med. 2014;17(11):1221-1225.

17. Ellsworth SG, Alcorn SR, Hales RK, McNutt TR, DeWeese TL, Smith TJ. Patterns of care among patients receiving radiation therapy for bone metastases at a large academic institution. Int J Radiat Oncol Biol Phys. 2014;89(5):1100-1105.

18. Bradley NM, Husted J, Sey MS, et al. Review of patterns of practice and patients’ preferences in the treatment of bone metastases with palliative radiotherapy. Support Care Cancer. 2007;15(4):373-385.

19. Haidukewych GJ. Metastatic disease around the hip: maintaining quality of life. J Bone Joint Surg Br. 2012;94(11 suppl A):22-25.

20. Mirels H. Metastatic disease in long bones. A proposed scoring system for diagnosing impending pathologic fractures. Clin Orthop Relat Res. 1989;(249):256-264.

21. Jacofsky DJ, Haidukewych GJ. Management of pathologic fractures of the proximal femur: state of the art. J Orthop Trauma. 2004;18(7):459-469.

22. Townsend PW, Rosenthal HG, Smalley SR, Cozad SC, Hassanein RE. Impact of postoperative radiation therapy and other perioperative factors on outcome after orthopedic stabilization of impending or pathologic fractures due to metastatic disease. J Clin Oncol. 1994;12(11):2345-2350.

23. Townsend PW, Smalley SR, Cozad SC, Rosenthal HG, Hassanein RE. Role of postoperative radiation therapy after stabilization of fractures caused by metastatic disease. Int J Radiat Oncol Biol Phys. 1995;31(1):43-49.

24. Farooki A. NCCN bone health task force: key recommendations. J Natl Compr Canc Netw. 2014;12(5 suppl):813-816.

25. Sejpal SV, Bhate A, Small W. Palliative radiation therapy in the management of brain metastases, spinal cord compression, and bone metastases. Semin Intervent Radiol. 2007;24(4):362-374.

26. Abrahm JL, Banffy MB, Harris MB. Spinal cord compression in patients with advanced metastatic cancer: “all I care about is walking and living my life.” JAMA. 2008;299(8):937-946.

27. Kim RY, Spencer SA, Meredith RF, et al. Extradural spinal cord compression: analysis of factors determining functional prognosis—prospective study. Radiology. 1990;176(1):279-282.

28. Kaloostian PE, Yurter A, Etame AB, Vrionis FD, Sciubba DM, Gokaslan ZL. Palliative strategies for the management of primary and metastatic spinal tumors. Cancer Control. 2014;21(2):140-143.

29. Graham PH, Capp A, Delaney G, et al. A pilot randomized comparison of dexamethasone 96 mg vs 16 mg per day for malignant spinal-cord compression treated by radiotherapy: TROG 01.05 Superdex study. Clin Oncol (R Coll Radiol). 2006;18(1):70-76.

30. Patchell RA, Tibbs PA, Regine WF, et al. Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. Lancet. 2005;366(9486):643-648.

31. Rades D, Huttenlocher S, Bajrovic A, et al. Surgery followed by radiotherapy versus radiotherapy alone for metastatic spinal cord compression from unfavorable tumors. Int J Radiat Oncol Biol Phys. 2011;81(5):e861-e868.

32. Maranzano E, Latini P. Effectiveness of radiation therapy without surgery in metastatic spinal cord compression: final results from a prospective trial. Int J Radiat Oncol Biol Phys. 1995;32(4):959-967.

33. Rades D, Fehlauer F, Schulte R, et al. Prognostic factors for local control and survival after radiotherapy of metastatic spinal cord compression. J Clin Oncol. 2006;24(21):3388-3393.

34. Howell DD, James JL, Hartsell WF, et al. Single-fraction radiotherapy versus multifraction radiotherapy for palliation of bone metastases-equivalent efficacy, less toxicity, more convenient: a subset analysis of Radiation Therapy Oncology Group trial 97-14. Cancer. 2013;119(4):888-896.

35. Wong J, Hird A, Kirou-Mauro, Napolskikh J, Chow E. Quality of life in brain metastases radiation trials: a literature review. Curr Oncol. 2008;15(5):25-45.

36. Nichols EM, Patchell RA, Regine WF, Kwok Y. Palliation of brain and spinal cord metastases. In: Halperin EC, Brady LW, Perez CA, Wazer DE, eds. Perez and Brady’s Principles and Practice of Radiation Oncology. 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2013:1974.

37. Zimm S, Wampler GL, Stablein D, Hazra T, Young HF. Intracerebral metastases in solid-tumor patients: natural history and results of treatment. Cancer. 1981;48(2):384-394.

38. Khuntia D, Brown P, Li J, Mehta MP. Whole-brain radiotherapy in the management of brain metastasis. J Clin Oncol. 2006;24(8):1295-1304.

39. Sundström JT, Minn H, Lertola KK, Nordman E. Prognosis of patients treated for intracranial metastases with whole-brain irradiation. Ann Med. 1998;30(3):296-299.

40. Tsao MN, Rades D, Wirth A, et al. Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es): an American Society for Radiation Oncology evidence-based guideline. Pract Radiat Oncol. 2012;2(3):210-225.

41. Gaspar L, Scott C, Rotman M, et al. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys. 1997;37(4):745-751.

42. Sperduto PW, Berkey B, Gaspar LE, Mehta M, Curran W. A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1,960 patients in the RTOG databases. Int J Radiat Oncol Biol Phys. 2008;70(2):510-514.

43. Sperduto PW, Kased N, Roberge D, et al. Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol. 2012;30(4):419-425.

44. Ryken TC, McDermott M, Robinson PD, et al. The role of steroids in the management of brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol. 2010;96(1):103-114.

45. Ruderman NB, Hall TC. Use of glucocorticoids in the palliative treatment of metastatic brain tumors. Cancer. 1965;18:298-306.

46. Kaloostian PE, Yurter A, Etame AB, Vrionis FD, Sciubba DM, Gokaslan ZL. Palliative strategies for the management of primary and metastatic spinal tumors. Cancer Control. 2014;21(2):140-143.

47. Horton J, Baxter DH, Olson KB. The management of metastases to the brain by irradiation and corticosteroids. Am J Roentgenol Radium Ther Nucl Med. 1971;111(2)334-336.

48. Wong J, Hird A, Zhang L, et al. Symptoms and quality of life in cancer patients with brain metastases following palliative radiotherapy. Int J Radiat Oncol Biol Phys. 2009;75(4):1125-1131.

49. Li J, Bentzen SM, Renschler M, Mehta MP. Regression after whole-brain radiation therapy for brain metastases correlates with survival and improved neurocognitive function. J Clin Oncol. 2007;25(10):1260-1266.

50. Andrews DW, Scott CB, Sperduto PW, et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004;363(9422):1665-1672.

51. Patchell RA, Tibbs PA, Walsh JW, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med. 1990;322(8):494-500.

52. Patchell RA, Tibbs PA, Regine WF, et al. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA. 1998;280(17):1485-1489.

53. Kocher M, Soffietti R, Abacioglu U, et al. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol. 2011;29(2):134-141.

54. Chang EL, Wefel JS, Hess KR, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009;10(11):1037-1044.

In recent years, there has been increasing interest in palliative care for patients with cancer at the end of life. Up to 23% of patients have metastatic disease at presentation, and symptoms from metastatic lesions can cause significant anxiety and impair patients’ quality of life (QOL). ¹

Palliative radiotherapy (RT) plays a valuable role in the management of metastatic disease to relieve tumor-related symptoms. Although palliative RT does not provide a chance for a cure, it improves QOL and may prolong survival time. ^2-4An estimated 20% to 50% of radiation courses are prescribed with palliative intent, because RT is highly effective in providing symptom relief, and the toxicity associated with palliative doses is typically mild. ^5,6 Palliative RT can be used to manage bone and brain metastases, prevent or treat spinal cord compression, and manage numerous tumor-related symptoms, such as pain and bleeding in patients with terminal cancer.

Palliative RT for bone and brain metastases is supported by high-quality evidence and is considered one of the most effective and cost-effective options available. ^7,8 This article aims to review the role of RT in treating 3 conditions commonly encountered in patients with metastatic disease—bone metastases, spinal cord compression, and brain metastases—and to emphasize the importance of timely integration of RT for optimal results.

Bone Metastases

About 80% of patients with metastatic solid tumors develop bone metastases, and about 350,000 deaths are linked to bone metastases in the U.S. each year. ⁹ Osseous
metastases can lead to pain, fracture, hypercalcemia, and spinal cord compression. The primary modality for treatment of pain and prevention of morbidity from bone metastases is external beam RT. ¹⁰

The likelihood of bone pain relief with palliative RT is 60% to 80%, and 30% to 40% of patients achieving complete pain relief. Randomized studies have shown multiple-dose and fractionation regimens provided effective symptom relief for bone metastases. Most commonly used regimens include a single fraction of 8 gray (Gy) delivered in 1 treatment, 20 Gy in 5 fractions delivered daily over 1 week, and 30 Gy in 10 fractions delivered over 2 weeks. Treatment with a single fraction improves access to treatment and patient convenience, whereas more prolonged courses have been associated with lower rates of retreatment. ^11,12 Regarding the higher rate of retreatment with single-fraction RT, no clear evidence exists that this is due to a less durable pain response or lower level of pain relief. ¹³

There has been recent interest in using predictive models to estimate life expectancy to avoid long courses of RT at the end of life. ^14,15 Shorter treatment courses of 8 Gyonce or 20 Gy in 5 fractions are particularly valuable for patients with a life expectancy < 3 months to avoid long courses of treatment, and thereby improve QOL as patients transition into hospice. A recent survey demonstrated that 93% of radiation oncologists within the VHA are willing to prescribe short courses of RT consisting of ≤ 6 fractions, and 76% have experience with single-fraction RT. ¹⁶ These findings are in contradiction to the findings in the non-VA radiation oncology community, in which < 10% of patients with uncomplicated bone metastases are treated with a single fraction. ^17,18