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First UK Prostate Stereotactic Body Radiotherapy (SBRT) Cohort: Prospective Outcomes with 2.5 Years’ Median Follow-up
Clinical Oncology 28 (2016) e9ee16 Contents lists available at ScienceDirect
Clinical Oncology journal homepage: www.clinicaloncologyonline.net
Early Real Life Experience of Radium 223 (Ra223) in Castrate Resistant Prostate Cancer (CRPC) C. Hague, C. Fisher, C. O’Hara, P. Elliott, J. Wylie, A. Choudhury, A. Tran, C. Coyle, J. Livsey, J. Logue The Christie NHS Foundation Trust, Manchester, UK
Purpose: Ra223 is an effective treatment in patients with CRPC both in improving symptomatic bone metastases and overall survival. We assessed the effect and tolerability of Ra223 in patients treated via the CDF in terms of both biochemical and clinical response. Methods: Retrospective analysis of CRPC patients treated with Ra223 via CDF between December 2013 and May 2015. Toxicities graded as per CTCAE 4. Results: 58 patients, median age 71 (54e84); median WHO PS 1 (0e2). 81% patients had documented CDF approval. Median number of cycles 5 (1e6), all prescribed at 50 mg/kg. All patients had symptomatic progressive bone disease. Pre Ra223 52%, 17% and 5% had previous docetaxel, bisphosphonates and strontium, respectively. 29 patients who had prior palliative radiotherapy to bone received Ra223 with a median time between radiotherapy to initiation of Ra223 of 433 days. 50% of patients had a documented symptomatic improvement with 5% developing a skeletal related event, mean time 218 days. Median PSA pre- versus post-treatment was 225 (95% CI 139.8, 320.8) and 418 (95% CI 272.4, 691.3). Median alkaline phosphatase (ALP) pre- versus post-treatment was 292 (95% CI 197.5, 378.7) and 138 (95% CI 103.8, 222.6). Median haemoglobin pre- versus post-treatment was 118 (95% CI 115, 222) and 103 (95% CI 98,113). Incidence of grade (G) 3 or 4 events was low with 2% G3 anaemia, 3% G3 neutropenia, 0% G3 thrombocytopenia and no documented episodes of neutropenic sepsis or osteonecrosis of the jaw. There were no treatment related deaths. 36/58 (62%) are alive; 16/58 (44%) alive with progressive disease. Median PFS was 7.23 months (95% CI 5.73, 7.93). Conclusion: Ra223 has a safe toxicity profile in heavily pre-treated CRPC patients. PSA response was discordant with clinical benefit but there is a suggestion ALP may be a useful adjunct in assessing treatment response.
First UK Prostate Stereotactic Body Radiotherapy (SBRT) Cohort: Prospective Outcomes with 2.5 Years’ Median Follow-up D. Henderson *, P. Ostler y, A. Tree *, P. Hoskin y, P. Dankulchai y, H. Taylor *, V. Khoo *, N. van As * * Royal Marsden Hospital, Sutton, UK y Mount Vernon Hospital, London, UK
Purpose: The UK-led phase III PACE trial is comparing SBRT for localised prostate cancer with current standards of care. Many UK centres are developing SBRT programmes to participate. Prospective outcome data in a UK setting are therefore informative. Methods: Patients were treated with SBRT outside the PACE trial. Dose fractionation was 36.25 Gy in five fractions to PTV (with prostate receiving 40 Gy) on consecutive or alternate days. Treatment was given at The Royal Marsden (RM) (45) and Mount Vernon Cancer Centre (36). PSA, RTOG and IPSS scores were prospectively recorded. Results: 81 patients were treated, 79 had analysable data. Median followup was 2.5 years. 10 patients (12%) received hormone therapy. The majority (76; 94%) were low/intermediate risk. Incidence of acute (<12 weeks) G2þ bladder and rectal toxicity was 30% and 22%, respectively. Incidence of late G2þ bladder and rectal toxicity was 13% and 11%, respectively. At last follow-up 6 patients (8%) had ongoing G2þ toxicity. 3 patients experienced
http://dx.doi.org/10.1016/j.clon.2015.12.001
late G3 toxicity (2 GU, 1 GI), only 1 ongoing. No G4þ toxicity was observed. 54 patients had analysable IPSS data. Median pre-treatment, maximum acute and maximum late IPSS scores were 6, 17 and 7, respectively. Median baseline PSA was 9 ng/ml. For patients with a minimum follow-up of 2 years (45), median PSA was 0.3 ng/ml. 18 patients had a benign PSA bounce. At RM, the first 24 patients were treated with alternate daily fractionation (median 10 days), the subsequent 21 patients were treated on consecutive week days (median 7 days). There was no significant difference in G2þ acute toxicity between the two groups (bladder 37% versus 29%; rectal 24% versus 30%). Conclusion: UK prostate SBRT outcomes are consistent with conventionally fractionated treatments. Consecutive daily fractionation appears well tolerated. It remains vital to evaluate prostate SBRT in a randomised trial.
Pre-treatment Lymphocytopaenia is a Valid Adverse Prognostic Factor in Muscle-invasive and Advanced Bladder Cancer N. Joseph *, C. Thompson y, S. Dovedi z, J. Lyons *, T. Elliott *, A. Choudhury * * The
Christie Hospital, The Christie NHS Foundation Trust, Manchester, UK y University Hospitals of Morecambe Bay NHS Foundation Trust, Morecambe, UK z Institute of Cancer Sciences, University of Manchester, Manchester, UK
Purpose: A low pre-treatment absolute lymphocyte count (ALC) may result from cytokines secreted by the tumour microenvironment in association with aggressive tumour biology. We sought to establish the prognostic significance of lymphocytopaenia in muscle-invasive bladder cancer (MIBC) treated with radical chemoradiotherapy, followed by validation in a cohort of advanced bladder cancer (ABC) patients treated with palliative chemotherapy. Methods: 74 patients with MIBC and 131 patients with ABC comprised the training and validation sets, respectively. ALC on the first day of treatment was recorded. Invasive local or systemic recurrence in the training set and all-cause mortality in the validation cohort were defined as survival end points. Receiver operating characteristic (ROC) curve analysis was utilised to determine the optimal cut-off for defining lymphocytopaenia in the training set followed by multivariable Cox regression analysis to evaluate its impact. Subsequently, the prognostic significance of lymphocytopaenia was assessed in a multivariable model of the validation cohort, followed by an evaluation of ALC as a continuous variable in this group. Results: An ALC of 1.45 109/l was determined to be the optimal cut-off on ROC curve analysis in the training set. Multivariate analysis revealed that only lymphocytopaenia was significantly associated with inferior diseasefree survival [hazard ratio (HR) 3.9, 95% confidence interval (CI) 1.4e10.6; P ¼ 0.003], after adjusting for anaemia, neutrophilia, tumour stage and presence of hydronephrosis. In the validation cohort, lymphocytopaenia (HR 1.6, CI 1.1e2.4; P ¼ 0.02) and performance status (HR 1.7, 1.0e2.7; P ¼ 0.047) were significant factors for inferior overall survival when analysed in a binary variable multivariate regression model adjusted for anaemia, neutrophilia and presence of bone or visceral metastases. ALC was the sole significant factor when analysed as a continuous variable. (HR 0.66, CI 0.5e0.87; P ¼ 0.02). Conclusion: Lymphocytopaenia is an independent, simple and valid prognostic factor in MIBC and ABC, possibly representing a state of cancer induced immune suppression driving tumour progression resulting in an inferior outcome.
Clinical Oncology journal homepage: www.clinicaloncologyonline.net
Early Real Life Experience of Radium 223 (Ra223) in Castrate Resistant Prostate Cancer (CRPC) C. Hague, C. Fisher, C. O’Hara, P. Elliott, J. Wylie, A. Choudhury, A. Tran, C. Coyle, J. Livsey, J. Logue The Christie NHS Foundation Trust, Manchester, UK
Purpose: Ra223 is an effective treatment in patients with CRPC both in improving symptomatic bone metastases and overall survival. We assessed the effect and tolerability of Ra223 in patients treated via the CDF in terms of both biochemical and clinical response. Methods: Retrospective analysis of CRPC patients treated with Ra223 via CDF between December 2013 and May 2015. Toxicities graded as per CTCAE 4. Results: 58 patients, median age 71 (54e84); median WHO PS 1 (0e2). 81% patients had documented CDF approval. Median number of cycles 5 (1e6), all prescribed at 50 mg/kg. All patients had symptomatic progressive bone disease. Pre Ra223 52%, 17% and 5% had previous docetaxel, bisphosphonates and strontium, respectively. 29 patients who had prior palliative radiotherapy to bone received Ra223 with a median time between radiotherapy to initiation of Ra223 of 433 days. 50% of patients had a documented symptomatic improvement with 5% developing a skeletal related event, mean time 218 days. Median PSA pre- versus post-treatment was 225 (95% CI 139.8, 320.8) and 418 (95% CI 272.4, 691.3). Median alkaline phosphatase (ALP) pre- versus post-treatment was 292 (95% CI 197.5, 378.7) and 138 (95% CI 103.8, 222.6). Median haemoglobin pre- versus post-treatment was 118 (95% CI 115, 222) and 103 (95% CI 98,113). Incidence of grade (G) 3 or 4 events was low with 2% G3 anaemia, 3% G3 neutropenia, 0% G3 thrombocytopenia and no documented episodes of neutropenic sepsis or osteonecrosis of the jaw. There were no treatment related deaths. 36/58 (62%) are alive; 16/58 (44%) alive with progressive disease. Median PFS was 7.23 months (95% CI 5.73, 7.93). Conclusion: Ra223 has a safe toxicity profile in heavily pre-treated CRPC patients. PSA response was discordant with clinical benefit but there is a suggestion ALP may be a useful adjunct in assessing treatment response.
First UK Prostate Stereotactic Body Radiotherapy (SBRT) Cohort: Prospective Outcomes with 2.5 Years’ Median Follow-up D. Henderson *, P. Ostler y, A. Tree *, P. Hoskin y, P. Dankulchai y, H. Taylor *, V. Khoo *, N. van As * * Royal Marsden Hospital, Sutton, UK y Mount Vernon Hospital, London, UK
Purpose: The UK-led phase III PACE trial is comparing SBRT for localised prostate cancer with current standards of care. Many UK centres are developing SBRT programmes to participate. Prospective outcome data in a UK setting are therefore informative. Methods: Patients were treated with SBRT outside the PACE trial. Dose fractionation was 36.25 Gy in five fractions to PTV (with prostate receiving 40 Gy) on consecutive or alternate days. Treatment was given at The Royal Marsden (RM) (45) and Mount Vernon Cancer Centre (36). PSA, RTOG and IPSS scores were prospectively recorded. Results: 81 patients were treated, 79 had analysable data. Median followup was 2.5 years. 10 patients (12%) received hormone therapy. The majority (76; 94%) were low/intermediate risk. Incidence of acute (<12 weeks) G2þ bladder and rectal toxicity was 30% and 22%, respectively. Incidence of late G2þ bladder and rectal toxicity was 13% and 11%, respectively. At last follow-up 6 patients (8%) had ongoing G2þ toxicity. 3 patients experienced
http://dx.doi.org/10.1016/j.clon.2015.12.001
late G3 toxicity (2 GU, 1 GI), only 1 ongoing. No G4þ toxicity was observed. 54 patients had analysable IPSS data. Median pre-treatment, maximum acute and maximum late IPSS scores were 6, 17 and 7, respectively. Median baseline PSA was 9 ng/ml. For patients with a minimum follow-up of 2 years (45), median PSA was 0.3 ng/ml. 18 patients had a benign PSA bounce. At RM, the first 24 patients were treated with alternate daily fractionation (median 10 days), the subsequent 21 patients were treated on consecutive week days (median 7 days). There was no significant difference in G2þ acute toxicity between the two groups (bladder 37% versus 29%; rectal 24% versus 30%). Conclusion: UK prostate SBRT outcomes are consistent with conventionally fractionated treatments. Consecutive daily fractionation appears well tolerated. It remains vital to evaluate prostate SBRT in a randomised trial.
Pre-treatment Lymphocytopaenia is a Valid Adverse Prognostic Factor in Muscle-invasive and Advanced Bladder Cancer N. Joseph *, C. Thompson y, S. Dovedi z, J. Lyons *, T. Elliott *, A. Choudhury * * The
Christie Hospital, The Christie NHS Foundation Trust, Manchester, UK y University Hospitals of Morecambe Bay NHS Foundation Trust, Morecambe, UK z Institute of Cancer Sciences, University of Manchester, Manchester, UK
Purpose: A low pre-treatment absolute lymphocyte count (ALC) may result from cytokines secreted by the tumour microenvironment in association with aggressive tumour biology. We sought to establish the prognostic significance of lymphocytopaenia in muscle-invasive bladder cancer (MIBC) treated with radical chemoradiotherapy, followed by validation in a cohort of advanced bladder cancer (ABC) patients treated with palliative chemotherapy. Methods: 74 patients with MIBC and 131 patients with ABC comprised the training and validation sets, respectively. ALC on the first day of treatment was recorded. Invasive local or systemic recurrence in the training set and all-cause mortality in the validation cohort were defined as survival end points. Receiver operating characteristic (ROC) curve analysis was utilised to determine the optimal cut-off for defining lymphocytopaenia in the training set followed by multivariable Cox regression analysis to evaluate its impact. Subsequently, the prognostic significance of lymphocytopaenia was assessed in a multivariable model of the validation cohort, followed by an evaluation of ALC as a continuous variable in this group. Results: An ALC of 1.45 109/l was determined to be the optimal cut-off on ROC curve analysis in the training set. Multivariate analysis revealed that only lymphocytopaenia was significantly associated with inferior diseasefree survival [hazard ratio (HR) 3.9, 95% confidence interval (CI) 1.4e10.6; P ¼ 0.003], after adjusting for anaemia, neutrophilia, tumour stage and presence of hydronephrosis. In the validation cohort, lymphocytopaenia (HR 1.6, CI 1.1e2.4; P ¼ 0.02) and performance status (HR 1.7, 1.0e2.7; P ¼ 0.047) were significant factors for inferior overall survival when analysed in a binary variable multivariate regression model adjusted for anaemia, neutrophilia and presence of bone or visceral metastases. ALC was the sole significant factor when analysed as a continuous variable. (HR 0.66, CI 0.5e0.87; P ¼ 0.02). Conclusion: Lymphocytopaenia is an independent, simple and valid prognostic factor in MIBC and ABC, possibly representing a state of cancer induced immune suppression driving tumour progression resulting in an inferior outcome.