4.x Oligometastases: evidence for dose-fractionation

Transcription

1 4.x Oligometastases: evidence for dose-fractionation Background 4.x.1. The oligometastatic state can be defined as 1-3 isolated metastatic sites, typically occurring more than six months after successful treatment of primary disease 1. In colorectal cancer (in addition to sarcoma and other sites), surgical treatment of oligometastatic disease (most frequently liver metastases), is associated with prolonged overall survival 2. Multiple single-arm studies have shown that stereotactic radiotherapy is effective and well tolerated in the oligometastatic setting, in multiple histologies and anatomical sites (see below). Thus, it may be deployed as an alternative to surgery, or where surgery is not possible. However, in this developing field, patients should be treated within clinical trials or Commissioning Through Evaluation processes. Treatment technique 4.x.2 It is not possible to discuss dose-fractionation without discussing treatment technique. The majority of evidence comes from stereotactic body radiotherapy (SBRT, or SABR stereotactic ablative radiotherapy). Developments in radiotherapy technology have allowed the safe delivery of an ablative dose in five or fewer fractions, with high-precision. Patients have been treated using dedicated stereotactic systems (such as Cyberknife) and using conventional gantry-based systems with stereotactic capability. The optimal system for delivery is unknown, but image guidance, either with implanted fiducials and/or soft tissue tomography, is essential. Organ dose constraints for 1-5 fractions can be found in the AAPM and Timmerman publications 3, 4. Evidence for dose-fractionation: 4.x.3 There is no randomised data, and no established consensus for dosefractionation in radiotherapy for oligometastatic disease. Recommendations have been derived from systematic reviews of non-randomised studies (prospective and retrospective), along with expert consensus. Oligometastases: bone (including spine) and lymph nodes 4.x.4 In this setting, treatment can expect to achieve a local control around 80% and progression free survival of approximately 20% at 2-3 years 1. In this review, patients who received a Biologically Equivalent Dose > 100Gy, and those with tumours 3cm had better outcomes. Patients have typically received three fractions, but many with spinal disease received a single fraction. Treatment is well tolerated, with myelopathy rates for spinal treatments being less than 1% in most series 5. Recommendations (Grade B): Three fraction treatment: 30-45Gy (10-15Gy per fraction) Single fraction treatment: 18-24Gy Page 1 of 5

2 (These doses many need to be reduced dependent on proximity of organs at risk.) It should be noted that the risk of vertebral compression fracture following spinal treatment rises significantly for dose per fraction above 19Gy (10% vs %) 6 (Grade B). Contouring for spinal treatment should be based on the expert consensus guidelines by Cox et al 7 (Grade D). A number of case series have reported experience in treating metastatic disease occurring in a pelvis or spinal region previously treated with conventionally fractionated radiotherapy 8. Treatment appears to provide good local control and is well tolerated, with a low rate of myelopathy. Recommendations for retreatment (Grade D): Pelvis: Spine: 30Gy/5# 20-30Gy/2-5# Lung oligometastatic disease 4.x.5 Lung oligometastases present a similar clinical problem to early-stage primary lung cancer, for which stereotactic treatment is a standard of care 9. Specifically for patients with oligometastases, a BED > 100Gy is associated with approximately 90% local control at 1-2 years 10. Although Timmerman et al 11 found a significant increase in toxicity when treating central lung tumours, other series have found no increase in toxicity when treating with more than three fractions Recommendations: Peripheral lung oligometastases: 48-54Gy/3# (Grade B) Central lung oligometastases: 48-55Gy/5# (Grade C) Liver oligometastatic disease 4.x.6 The use of surgery and radiofrequency ablation to treat liver oligometastases is well established. For colorectal liver tumours under 6cm in diameter, local control above 90% at 1 year can be achieved with stereotactic doses of at least 48Gy in 3# 15. This analysis included patients who were heavily pre-treated with systemic therapy. Further reviews have indicated this dose is effective in other tumour types, with grade 3-4 toxicity of 1-10% 16, 17. Recommendation (Grade B): Liver oligometastases: 45-50Gy in 3# Adrenal oligometastatic disease Page 2 of 5

3 Due to a rich sinusoidal blood supply, adrenal metastases are freqeuently observed in patients with melanoma, breast, lung, kidney and gastrointestinal tumours. Based on observations of enhanced survival in patients undergoing adrenalectomy for oligometastatic disease, stereotactic radiotherapy has also been been utilised. Local control rates vary from 55% to 90% with doses ranging from 16Gy in 4 fractions to 50Gy in 10 fractions 18,19. Recommendation (Grade D): Adrenal oligometastases: 45 Gy in 3# Conclusions 4.x.8 There is good evidence that stereotactic radiotherapy for oligometastatic disease is well tolerated and effective, and that a BED above 100Gy should be the aim of treatment, while respect organ tolerance. However, in the absence of randomised evidence and a clear consensus on dose fractionation, patients should be treated in clinical trials or the Commissioning Through Evaluation process. Page 3 of 5

4 References 1. Tree AC, Khoo VS, Eeles RA, Ahmed M, Dearnaley DP, Hawkins MA, et al. Stereotactic body radiotherapy for oligometastases. Lancet Oncol. 2013; 14(1): e Weichselbaum RR, Hellman S. Oligometastases revisited. Nat Rev Clin Oncol. 2011; 8(6): Timmerman RD. An overview of hypofractionation and introduction to this issue of seminars in radiation oncology. Semin Radiat Oncol. 2008; 18(4): Benedict SH, Yenice KM, Followill D, Galvin JM, Hinson W, Kavanagh B, et al. Stereotactic body radiation therapy: the report of AAPM Task Group 101. Med Phys. 2010; 37(8): Bhattacharya IS, Hoskin PJ. Stereotactic Body Radiotherapy for Spinal and Bone Metastases. Clin Oncol (R Coll Radiol) Sahgal A, Atenafu EG, Chao S, Al-Omair A, Boehling N, Balagamwala EH, et al. Vertebral compression fracture after spine stereotactic body radiotherapy: a multi-institutional analysis with a focus on radiation dose and the spinal instability neoplastic score. J Clin Oncol. 2013; 31(27): Cox BW, Spratt DE, Lovelock M, Bilsky MH, Lis E, Ryu S, et al. International Spine Radiosurgery Consortium consensus guidelines for target volume definition in spinal stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2012; 83(5): e Mantel F, Flentje M, Guckenberger M. Stereotactic body radiation therapy in the re-irradiation situation--a review. Radiat Oncol. 2013; 8: Solda F, Lodge M, Ashley S, Whitington A, Goldstraw P, Brada M. Stereotactic radiotherapy (SABR) for the treatment of primary non-small cell lung cancer; systematic review and comparison with a surgical cohort. Radiother Oncol. 2013; 109(1): Siva S, MacManus M, Ball D. Stereotactic radiotherapy for pulmonary oligometastases: a systematic review. J Thorac Oncol. 2010; 5(7): Timmerman R, McGarry R, Yiannoutsos C, Papiez L, Tudor K, DeLuca J, et al. Excessive toxicity when treating central tumors in a phase II study of stereotactic body radiation therapy for medically inoperable early-stage lung cancer. J Clin Oncol. 2006; 24(30): Mangona VS, Aneese AM, Marina O, Hymas RV, Ionascu D, Robertson JM, et al. Toxicity After Central versus Peripheral Lung Stereotactic Body Radiation Therapy: A Propensity Score Matched-Pair Analysis. Int J Radiat Oncol Biol Phys Nuyttens JJ, van der Voort van Zyp NC, Praag J, Aluwini S, van Klaveren RJ, Verhoef C, et al. Outcome of four-dimensional stereotactic radiotherapy for centrally located lung tumors. Radiother Oncol. 2012; 102(3): Chang JY, Balter PA, Dong L, Yang Q, Liao Z, Jeter M, et al. Stereotactic body radiation therapy in centrally and superiorly located stage I or isolated recurrent non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2008; 72(4): Chang DT, Swaminath A, Kozak M, Weintraub J, Koong AC, Kim J, et al. Stereotactic body radiotherapy for colorectal liver metastases: a pooled analysis. Cancer. 2011; 117(17): Aitken KL, Hawkins MA. Stereotactic Body Radiotherapy for Liver Metastases. Clin Oncol (R Coll Radiol) Page 4 of 5

5 17. Hoyer M, Swaminath A, Bydder S, Lock M, Mendez Romero A, Kavanagh B, et al. Radiotherapy for liver metastases: a review of evidence. Int J Radiat Oncol Biol Phys. 2012; 82(3): Chawla S, Chen Y, Katz AW, Muhs AG, Philip A, Okunieff P, Milano MT. Stereotactic body radiotherapy for treatment of adrenal metastases. Int J Radiat Oncol Biol Phys Sep 1;75(1): Casamassima F, Livi L, Masciullo S, Menichelli C, Masi L, Meattini I, Bonucci I, Agresti B, Simontacchi G, Doro R. Stereotactic radiotherapy for adrenal gland metastases: university of Florence experience. Int J Radiat Oncol Biol Phys Feb 1;82(2): Page 5 of 5