Letters / Clinical Oncology 27 (2015) 542e544
observational study that purports to show improved survival in patients with liver metastases after SABR [3]. Although large, this study will probably have major selection bias and is not good evidence for a survival effect. Second, they cited the meta-analysis by Fairchild et al. [4] of palliative thoracic radiotherapy for non-small cell lung cancer, suggesting that a higher dose of radiotherapy gives longer survival. This is a totally different clinical situation that has little relevance to the use SBRT for metastases. Also, an update of the Cochrane review on palliative radiotherapy for non-small cell lung cancer [5] includes a meta-analysis that does not confirm that higher dose/fractionation increases 1 year survival. SBRT, like surgery, for pulmonary metastases remains an unproven intervention [6]. Clinical oncologists should not use it, especially in patients who have been turned down for surgery, because there will be immediate and late adverse effects and the palliative and survival benefit is unproven. They should instead ensure that their surgical colleagues participate in the PULMiCC trial.
543
References [1] Hanna GG, Landau D. Stereotactic body radiotherapy for oligometastatic disease. Clin Oncol (R Coll Radiol) 2015;27: 290e297. [2] Pulmonary metastasectomy in colorectal cancer. Available at: http://public.ukcrn.org.uk/search/StudyDetail.aspx? StudyID¼9018. [3] Rusthoven KE, Kavanagh BD, Cardenes R, et al. Multi-institutional phase I/II study of individualized stereotactic body radiotherapy of liver metastases. Acta Oncol 2009;27: 1572e1578. [4] Fairchild A, Harris K, Barnes E, et al. Palliative thoracic radiotherapy for lung cancer: a systematic review. J Clin Oncol 2008; 26:4001e4011. [5] Stevens R, Macbeth F, Toy E, et al. Palliative radiotherapy regimens for patients with thoracic symptoms from non-small cell lung cancer. Cochrane Database System Rev 2015;1:CD002143. http://dx.doi.org/10.1002/14651858.CD002143.pub4. [6] Treasure T, Milosevic M, Fiorentino F, et al. Pulmonary metastasectomy: what is the practice and where is the evidence for effectiveness. Thorax 2014;69:946e949.
F. Macbeth*, T. Treasurey * Wales Cancer Trials Unit, Cardiff University, Cardiff, UK y Clinical Operational Research Unit, University College London, London, UK DOI of original article: http://dx.doi.org/10.1016/j.clon.2015.02.003 http://dx.doi.org/10.1016/j.clon.2015.06.004 Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Re: Stereotactic Body Radiotherapy for Oligometastatic Disease Sir d We thank Macbeth and Treasure for their letter [1] and the points they raise therein and we are grateful for the opportunity to provide a response. We firstly acknowledge and apologise for our error in describing the PULMiCC study as complete, when in fact only the feasibility cohort has completed accrual [2]. We strongly recommend that all potential investigators support this important study in oligometastatic disease. The correspondents seem to have mistakenly come to the conclusion from our paper that we have made clinical recommendations. This is simply not the case. The introduction makes it absolutely clear we make no such recommendation, rather we recognise that there is a ‘paucity of evidence available demonstrating a clinical benefit [3]’. In our conclusion we clearly state that we hope that studies of stereotactic body radiotherapy (SBRT) in oligometastatic disease ‘will provide much needed information on both appropriate patient selection for SBRT treatment and the impact of SBRT for patients with oligometastatic disease [3]’. If definitive evidence of clinical benefit existed for extra-cranial SBRT in the treatment of oligometastatic disease, then difficulties would arise in conducting clinical studies such as CORE or SARON. Considering any potential mechanism of the benefit of SBRT in oligometastatic disease, MacBeth and Treasure [1]
write that ‘it is illogical to expect the treatment of asymptomatic and non-life-threatening metastases is likely to change overall survival’. We agree with Macbeth and Treasure that there is no definitive level 1 evidence to support this. The PULMiCC study is based on the hypothesis that ablative treatment of asymptomatic lung metastases (albeit with a more invasive and morbid surgical ablative intervention) might affect survival in patients with colorectal cancer. Without conducting studies such as PULMiCC, SARON and CORE, we will never know if local therapy has an impact on patients with such metastases. In our paper, our discussion regarding the role of radiotherapy in patients with metastatic non-small cell lung cancer explores the relationship of local control of metastatic disease with radiotherapy dose. At the time of writing our article, the Cochrane review cited was not available and we thank Macbeth and Treasure for bringing this to our attention [4]. We agree with Macbeth and Treasure that, for SBRT and palliative radiotherapy in the treatment of non-small cell lung cancer, the mechanisms of any possible clinical benefit may be different. However, given the high-quality early phase trial evidence of prolonged survival where SBRT is used for oligoprogression, the potential of SBRT for oligometastatic disease at presentation requires investigation [5].
544
Letters / Clinical Oncology 27 (2015) 542e544
In summary, our paper was written to aid the interpretation of ongoing trials of SBRT in oligometastatic disease and to discuss possible mechanisms that may lead to clinical benefit. We strongly encourage clinicians to support the studies of SBRT and other treatment modalities in oligometastatic disease in which we hope the UK can make a significant contribution to the global evidence. G.G. Hanna*, D. Landauy * Centre for Cancer Research and Cell Biology, Queen’s University of Belfast, Belfast, UK y Department of Oncology, Guys and St Thomas’ Hospital, Division of Imaging Sciences, King’s College London, London, UK
References [1] Macbeth F, Treasure T. Stereotactic body radiotherapy for pulmonary metastases. Clin Oncol 2015;27(9):542e543. [2] Network UCR. UK Clinical Research Network Study Portfolio PulMICC Study. Available at: http://public.ukcrn.org.uk/search/ StudyDetail.aspx?StudyID¼9018 [last accessed 03.06.15]. [3] Hanna GG, Landau D. Stereotactic body radiotherapy for oligometastatic disease. Clin Oncol 2015;27(5):290e297. [4] Stevens R, Macbeth F, Toy E, et al. Palliative radiotherapy regimens for patients with thoracic symptoms from non-small cell lung cancer. Cochrane Database Syst Rev 2015;1:CD002143. http://dx.doi.org/10.1002/14651858.CD002143.pub4. [5] Iyengar P, Kavanagh BD, Wardak Z, et al. Phase II trial of stereotactic body radiation therapy combined with erlotinib for patients with limited but progressive metastatic non-smallcell lung cancer. J Clin Oncol 2014;32(34):3824e3830.
DOI of original article: http://dx.doi.org/10.1016/j.clon.2015.06.004 http://dx.doi.org/10.1016/j.clon.2015.06.011 Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Pathological Response to Preoperative Treatment as a Predictor of Cancer Outcome in the Treatment of Soft-tissue Sarcoma Sir d We read with interest the recent letter by Panwar and Sankaye [1] advocating the development of a clinical trial to address the timing of radiotherapy in patients with extremity soft-tissue sarcoma. An important advantage of neoadjuvant radiotherapy is the availability of tissue for both prognostic and predictive biomarker research. In 2014, Mullen et al. [2] published a series of 113 patients with soft-tissue sarcoma who underwent neoadjuvant chemoradiotherapy followed by surgery. On reviewing postoperative histology, they found no statistically significant difference in local recurrence and survival rates between patients with 95% versus
observational study that purports to show improved survival in patients with liver metastases after SABR [3]. Although large, this study will probably have major selection bias and is not good evidence for a survival effect. Second, they cited the meta-analysis by Fairchild et al. [4] of palliative thoracic radiotherapy for non-small cell lung cancer, suggesting that a higher dose of radiotherapy gives longer survival. This is a totally different clinical situation that has little relevance to the use SBRT for metastases. Also, an update of the Cochrane review on palliative radiotherapy for non-small cell lung cancer [5] includes a meta-analysis that does not confirm that higher dose/fractionation increases 1 year survival. SBRT, like surgery, for pulmonary metastases remains an unproven intervention [6]. Clinical oncologists should not use it, especially in patients who have been turned down for surgery, because there will be immediate and late adverse effects and the palliative and survival benefit is unproven. They should instead ensure that their surgical colleagues participate in the PULMiCC trial.
543
References [1] Hanna GG, Landau D. Stereotactic body radiotherapy for oligometastatic disease. Clin Oncol (R Coll Radiol) 2015;27: 290e297. [2] Pulmonary metastasectomy in colorectal cancer. Available at: http://public.ukcrn.org.uk/search/StudyDetail.aspx? StudyID¼9018. [3] Rusthoven KE, Kavanagh BD, Cardenes R, et al. Multi-institutional phase I/II study of individualized stereotactic body radiotherapy of liver metastases. Acta Oncol 2009;27: 1572e1578. [4] Fairchild A, Harris K, Barnes E, et al. Palliative thoracic radiotherapy for lung cancer: a systematic review. J Clin Oncol 2008; 26:4001e4011. [5] Stevens R, Macbeth F, Toy E, et al. Palliative radiotherapy regimens for patients with thoracic symptoms from non-small cell lung cancer. Cochrane Database System Rev 2015;1:CD002143. http://dx.doi.org/10.1002/14651858.CD002143.pub4. [6] Treasure T, Milosevic M, Fiorentino F, et al. Pulmonary metastasectomy: what is the practice and where is the evidence for effectiveness. Thorax 2014;69:946e949.
F. Macbeth*, T. Treasurey * Wales Cancer Trials Unit, Cardiff University, Cardiff, UK y Clinical Operational Research Unit, University College London, London, UK DOI of original article: http://dx.doi.org/10.1016/j.clon.2015.02.003 http://dx.doi.org/10.1016/j.clon.2015.06.004 Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Re: Stereotactic Body Radiotherapy for Oligometastatic Disease Sir d We thank Macbeth and Treasure for their letter [1] and the points they raise therein and we are grateful for the opportunity to provide a response. We firstly acknowledge and apologise for our error in describing the PULMiCC study as complete, when in fact only the feasibility cohort has completed accrual [2]. We strongly recommend that all potential investigators support this important study in oligometastatic disease. The correspondents seem to have mistakenly come to the conclusion from our paper that we have made clinical recommendations. This is simply not the case. The introduction makes it absolutely clear we make no such recommendation, rather we recognise that there is a ‘paucity of evidence available demonstrating a clinical benefit [3]’. In our conclusion we clearly state that we hope that studies of stereotactic body radiotherapy (SBRT) in oligometastatic disease ‘will provide much needed information on both appropriate patient selection for SBRT treatment and the impact of SBRT for patients with oligometastatic disease [3]’. If definitive evidence of clinical benefit existed for extra-cranial SBRT in the treatment of oligometastatic disease, then difficulties would arise in conducting clinical studies such as CORE or SARON. Considering any potential mechanism of the benefit of SBRT in oligometastatic disease, MacBeth and Treasure [1]
write that ‘it is illogical to expect the treatment of asymptomatic and non-life-threatening metastases is likely to change overall survival’. We agree with Macbeth and Treasure that there is no definitive level 1 evidence to support this. The PULMiCC study is based on the hypothesis that ablative treatment of asymptomatic lung metastases (albeit with a more invasive and morbid surgical ablative intervention) might affect survival in patients with colorectal cancer. Without conducting studies such as PULMiCC, SARON and CORE, we will never know if local therapy has an impact on patients with such metastases. In our paper, our discussion regarding the role of radiotherapy in patients with metastatic non-small cell lung cancer explores the relationship of local control of metastatic disease with radiotherapy dose. At the time of writing our article, the Cochrane review cited was not available and we thank Macbeth and Treasure for bringing this to our attention [4]. We agree with Macbeth and Treasure that, for SBRT and palliative radiotherapy in the treatment of non-small cell lung cancer, the mechanisms of any possible clinical benefit may be different. However, given the high-quality early phase trial evidence of prolonged survival where SBRT is used for oligoprogression, the potential of SBRT for oligometastatic disease at presentation requires investigation [5].
544
Letters / Clinical Oncology 27 (2015) 542e544
In summary, our paper was written to aid the interpretation of ongoing trials of SBRT in oligometastatic disease and to discuss possible mechanisms that may lead to clinical benefit. We strongly encourage clinicians to support the studies of SBRT and other treatment modalities in oligometastatic disease in which we hope the UK can make a significant contribution to the global evidence. G.G. Hanna*, D. Landauy * Centre for Cancer Research and Cell Biology, Queen’s University of Belfast, Belfast, UK y Department of Oncology, Guys and St Thomas’ Hospital, Division of Imaging Sciences, King’s College London, London, UK
References [1] Macbeth F, Treasure T. Stereotactic body radiotherapy for pulmonary metastases. Clin Oncol 2015;27(9):542e543. [2] Network UCR. UK Clinical Research Network Study Portfolio PulMICC Study. Available at: http://public.ukcrn.org.uk/search/ StudyDetail.aspx?StudyID¼9018 [last accessed 03.06.15]. [3] Hanna GG, Landau D. Stereotactic body radiotherapy for oligometastatic disease. Clin Oncol 2015;27(5):290e297. [4] Stevens R, Macbeth F, Toy E, et al. Palliative radiotherapy regimens for patients with thoracic symptoms from non-small cell lung cancer. Cochrane Database Syst Rev 2015;1:CD002143. http://dx.doi.org/10.1002/14651858.CD002143.pub4. [5] Iyengar P, Kavanagh BD, Wardak Z, et al. Phase II trial of stereotactic body radiation therapy combined with erlotinib for patients with limited but progressive metastatic non-smallcell lung cancer. J Clin Oncol 2014;32(34):3824e3830.
DOI of original article: http://dx.doi.org/10.1016/j.clon.2015.06.004 http://dx.doi.org/10.1016/j.clon.2015.06.011 Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Pathological Response to Preoperative Treatment as a Predictor of Cancer Outcome in the Treatment of Soft-tissue Sarcoma Sir d We read with interest the recent letter by Panwar and Sankaye [1] advocating the development of a clinical trial to address the timing of radiotherapy in patients with extremity soft-tissue sarcoma. An important advantage of neoadjuvant radiotherapy is the availability of tissue for both prognostic and predictive biomarker research. In 2014, Mullen et al. [2] published a series of 113 patients with soft-tissue sarcoma who underwent neoadjuvant chemoradiotherapy followed by surgery. On reviewing postoperative histology, they found no statistically significant difference in local recurrence and survival rates between patients with 95% versus
