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Early Cessation of Docetaxel Chemotherapy may Compromise Survival Benefit in Advanced Prostate Cancer
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Abstracts / Clinical Oncology 26 (2014) e1ee7
Results: 235 patients were eligible, of which 63 received second-line chemotherapy. Of those with a recorded value, 65% had a raised sb-HCG level (2 IU/l) prior to second-line chemotherapy and 50% on completion of treatment. Patients with a low sb-HCG level on completion of second-line chemotherapy had longer overall survival (median 1.78 versus 0.29 years, P ¼ 0.003) and progression-free survival (median 0.67 versus 0.15 years, P ¼ 0.017). Conclusion: Post-chemotherapy sb-HCG level is an independent prognostic factor for TCCUT for all lines of conventional systemic therapy. Raised levels after chemotherapy identify patients who will have a relatively poor outcome. Prospective evaluation of a potential role in treatment stratification strategies is warranted.
Evaluation of Prostate Brachytherapy Post-implant V100 Dosimetry Through an Institutional Change in Treatment Planning Software N. De Silva, S. Brook, S. Russell Addenbrookes Hospital, Cambridge, UK
Introduction: Our department has considerable experience delivering low dose rate prostate brachytherapy using I125 seeds. Up until June 2012, we used the Sonographic Planning of Oncologic Treatment (SPOT) Pro software for treatment planning. After this date, we moved to the Oncentra Prostate Planning system, which employs a hybrid Inverse Planning Simulated Annealing (IPSA) algorithm. We evaluated the impact of changing our software planning system on our brachytherapy treatments. Materials and methods: This was a retrospective study of prospectively collected data comparing 30 patients before and after the introduction of the Oncentra system. We compared patient prostate volumes, the number of seeds and needles used per treatment, as well as the post-dosimetry D90. The unpaired t-test was used to compare the means. The ManneWhitney Utest was used to compare the post-dosimetry V100 as these data were negatively skewed. Results: Mean prostate volumes in the patients treated were not significantly different (mean 38.8 ml versus 39.43 for diagnostic USS and 39.79 versus 42.77 for the planning system). A similar number of seeds (67.77 versus 70.93) and needles (25.03 versus 24.26) were used with both software systems. The post-implant dosimetry V100 was significantly different between the study groups (median 94.94% versus 92.55%; P ¼ 0.0016). The first 15 patients treated with the Oncentra system had considerably lower postdosimetry V100. Examination of these data through time demonstrated that this variance resolved with ongoing familiarity with the software system (standard deviation for first 15 patients was 7.98 versus 6.5 for the next 15). This did not translate to a significant difference in the D90 (mean 163.5 Gy pre- and 150 Gy post-Oncentra). Conclusion: Changing brachytherapy treatment planning software can cause significant differences in the post-dosimetry V100. When changing planning software, there is a learning curve of about 15 patients to achieve optimal post-implant dosimetry.
Early Cessation of Docetaxel Chemotherapy may Compromise Survival Benefit in Advanced Prostate Cancer P. Dickinson *, J. Malik y, A. Sivanandan *, F. Slevin *, T. Elliott * * The Christie NHS Foundation Trust, Manchester, UK y Edinburgh Cancer Centre, NHS Lothian, Edinburgh, UK
Introduction: The Trapeze/TAX327/SWOG9916 trials delivered 6/10/12 cycles of 3-weekly docetaxel chemotherapy to patients with CRPC. The optimum number of cycles is not known. Newer treatments such as abiraterone are of proven clinical benefit and have a more favourable toxicity profile. If fewer cycles of docetaxel were delivered patients could be changed to a less toxic treatment sooner. We compared the outcomes of patients who electively received only 6 cycles of docetaxel with those who were planned to receive up to 10 cycles. Materials and methods: Retrospective data were collected for men who received docetaxel chemotherapy at The Christie NHS Foundation Trust between 2005 and 2011. Survival was the interval between the first dose of chemotherapy and death.
Results: Data were collected for 333 patients. At the commencement of chemotherapy, all patients had a KPS > 70%, median age was 67 years (range 49e81) and median PSA was 242 mg/l. At the time of analysis there had been 292 deaths. Median survival for the whole group was 403 days. 134 patients electively completed chemotherapy following 6 planned cycles of docetaxel and had not experienced dose-limiting toxicity or disease progression. 68 men received 7e10 cycles of docetaxel following a change in practice to increase the number of cycles delivered to a maximum of 10. The median survival for men who received 6 cycles of chemotherapy was 462 days. The median survival for men who received 7e10 cycles of chemotherapy was significantly longer at 635 days (P ¼ 0.019). Conclusion: Men who received 7e10 cycles of chemotherapy had a significantly better survival than those who electively stopped chemotherapy following 6 cycles. Our data suggest that men should receive up to 10 cycles of docetaxel if they are able to tolerate treatment. Stopping chemotherapy prematurely to commence an alternative treatment may deny some men maximum survival benefit from docetaxel chemotherapy.
A Novel Tumour Suppressor Gene, AIMP3, is Lost in Bladder Cancer and Loss of Expression Sensitises Bladder Cancer to Chemo/radiotherapy in vitro P. Gurung, A. Veerakumarasivam, M. Williamson, N. Counsell, S. Short, A. Feber University College London Hospitals NHS Foundation Trust, London, UK
Introduction: AIMP3 (p18/EEF1E1), a novel tumour suppressor gene (TSG), interacts with ATM-p53 and causes spontaneous cancers in haploinsufficient mice. We identified loss of AIMP3 following a promoter-methylation screen for low-level expressing genes in bladder cancer (BCa). The aim of this study was to characterise the phenotype of AIMP3 deficient cells. Materials and methods: Expression array data on BCa specimens was screened using a promoter-methylation library to identify potential TSGs whose expression may be lost in BCa. Expression (Western) and nuclear localisation (immunofluorescence) were assessed in T24, 253J, RT112 and RT4 BCa cell lines (HeLa as control). AIMP3 was targeted using siRNA and cytotoxicity assessed using colony forming assay (CFA) (including RT112CP, a cisplatin-resistant variant of RT112). Expression was characterised by immunostaining a tissue microarray (TMA) representative of BCa grades and stages. Results: AIMP3 was constitutively expressed in the cell lines and was lower for T24 (high-grade) cells compared with RT4 (P < 0.01; two-tailed t-test). AIMP3 was expressed in normal urothelium and loss in BCa was related to grade and stage. AIMP3 localised to the nuclear compartment 1 h following irradiation and total expression increased after 72 h. Knockdown of AIMP3 increased clonogenic survival following irradiation (P < 0.04 in T24, RT112 and RT4). Targeting AIMP3 did not alter cisplatin sensitivity in RT112, but had a significant effect in RT112CP (P ¼ 0.01). Conclusion: We confirm loss of expression of the novel TSG, AIMP3, in BCa. AIMP3 migrates to the nucleus upon DNA damage and targeting the gene in vitro promotes cell survival and resistance to radiotherapy and chemotherapy.
Transperineal MRI-targeted Biopsy Versus Transperineal Template Prostate Mapping Biopsy in the Detection of Radio-recurrent Prostate Cancer A. Kanthabalan, M. Abl-Azzeez, M. Arya, A. Freeman, S. Punwani, H. Ahmed University College London Hospitals NHS Foundation Trust, London, UK
Introduction: External beam radiotherapy (EBRT) is effective in treating early localised prostate cancer. However, one third of men will experience biochemical failure by 5 years. Most men are expectantly managed with delayed hormones, yet half of these men have localised recurrence, which may be suitable for local salvage therapy. Multi-parametric magnetic resonance imaging (mpMRI) has shown high performance characteristics in detecting localised recurrence. We aimed to compare the cancer detection
Abstracts / Clinical Oncology 26 (2014) e1ee7
Results: 235 patients were eligible, of which 63 received second-line chemotherapy. Of those with a recorded value, 65% had a raised sb-HCG level (2 IU/l) prior to second-line chemotherapy and 50% on completion of treatment. Patients with a low sb-HCG level on completion of second-line chemotherapy had longer overall survival (median 1.78 versus 0.29 years, P ¼ 0.003) and progression-free survival (median 0.67 versus 0.15 years, P ¼ 0.017). Conclusion: Post-chemotherapy sb-HCG level is an independent prognostic factor for TCCUT for all lines of conventional systemic therapy. Raised levels after chemotherapy identify patients who will have a relatively poor outcome. Prospective evaluation of a potential role in treatment stratification strategies is warranted.
Evaluation of Prostate Brachytherapy Post-implant V100 Dosimetry Through an Institutional Change in Treatment Planning Software N. De Silva, S. Brook, S. Russell Addenbrookes Hospital, Cambridge, UK
Introduction: Our department has considerable experience delivering low dose rate prostate brachytherapy using I125 seeds. Up until June 2012, we used the Sonographic Planning of Oncologic Treatment (SPOT) Pro software for treatment planning. After this date, we moved to the Oncentra Prostate Planning system, which employs a hybrid Inverse Planning Simulated Annealing (IPSA) algorithm. We evaluated the impact of changing our software planning system on our brachytherapy treatments. Materials and methods: This was a retrospective study of prospectively collected data comparing 30 patients before and after the introduction of the Oncentra system. We compared patient prostate volumes, the number of seeds and needles used per treatment, as well as the post-dosimetry D90. The unpaired t-test was used to compare the means. The ManneWhitney Utest was used to compare the post-dosimetry V100 as these data were negatively skewed. Results: Mean prostate volumes in the patients treated were not significantly different (mean 38.8 ml versus 39.43 for diagnostic USS and 39.79 versus 42.77 for the planning system). A similar number of seeds (67.77 versus 70.93) and needles (25.03 versus 24.26) were used with both software systems. The post-implant dosimetry V100 was significantly different between the study groups (median 94.94% versus 92.55%; P ¼ 0.0016). The first 15 patients treated with the Oncentra system had considerably lower postdosimetry V100. Examination of these data through time demonstrated that this variance resolved with ongoing familiarity with the software system (standard deviation for first 15 patients was 7.98 versus 6.5 for the next 15). This did not translate to a significant difference in the D90 (mean 163.5 Gy pre- and 150 Gy post-Oncentra). Conclusion: Changing brachytherapy treatment planning software can cause significant differences in the post-dosimetry V100. When changing planning software, there is a learning curve of about 15 patients to achieve optimal post-implant dosimetry.
Early Cessation of Docetaxel Chemotherapy may Compromise Survival Benefit in Advanced Prostate Cancer P. Dickinson *, J. Malik y, A. Sivanandan *, F. Slevin *, T. Elliott * * The Christie NHS Foundation Trust, Manchester, UK y Edinburgh Cancer Centre, NHS Lothian, Edinburgh, UK
Introduction: The Trapeze/TAX327/SWOG9916 trials delivered 6/10/12 cycles of 3-weekly docetaxel chemotherapy to patients with CRPC. The optimum number of cycles is not known. Newer treatments such as abiraterone are of proven clinical benefit and have a more favourable toxicity profile. If fewer cycles of docetaxel were delivered patients could be changed to a less toxic treatment sooner. We compared the outcomes of patients who electively received only 6 cycles of docetaxel with those who were planned to receive up to 10 cycles. Materials and methods: Retrospective data were collected for men who received docetaxel chemotherapy at The Christie NHS Foundation Trust between 2005 and 2011. Survival was the interval between the first dose of chemotherapy and death.
Results: Data were collected for 333 patients. At the commencement of chemotherapy, all patients had a KPS > 70%, median age was 67 years (range 49e81) and median PSA was 242 mg/l. At the time of analysis there had been 292 deaths. Median survival for the whole group was 403 days. 134 patients electively completed chemotherapy following 6 planned cycles of docetaxel and had not experienced dose-limiting toxicity or disease progression. 68 men received 7e10 cycles of docetaxel following a change in practice to increase the number of cycles delivered to a maximum of 10. The median survival for men who received 6 cycles of chemotherapy was 462 days. The median survival for men who received 7e10 cycles of chemotherapy was significantly longer at 635 days (P ¼ 0.019). Conclusion: Men who received 7e10 cycles of chemotherapy had a significantly better survival than those who electively stopped chemotherapy following 6 cycles. Our data suggest that men should receive up to 10 cycles of docetaxel if they are able to tolerate treatment. Stopping chemotherapy prematurely to commence an alternative treatment may deny some men maximum survival benefit from docetaxel chemotherapy.
A Novel Tumour Suppressor Gene, AIMP3, is Lost in Bladder Cancer and Loss of Expression Sensitises Bladder Cancer to Chemo/radiotherapy in vitro P. Gurung, A. Veerakumarasivam, M. Williamson, N. Counsell, S. Short, A. Feber University College London Hospitals NHS Foundation Trust, London, UK
Introduction: AIMP3 (p18/EEF1E1), a novel tumour suppressor gene (TSG), interacts with ATM-p53 and causes spontaneous cancers in haploinsufficient mice. We identified loss of AIMP3 following a promoter-methylation screen for low-level expressing genes in bladder cancer (BCa). The aim of this study was to characterise the phenotype of AIMP3 deficient cells. Materials and methods: Expression array data on BCa specimens was screened using a promoter-methylation library to identify potential TSGs whose expression may be lost in BCa. Expression (Western) and nuclear localisation (immunofluorescence) were assessed in T24, 253J, RT112 and RT4 BCa cell lines (HeLa as control). AIMP3 was targeted using siRNA and cytotoxicity assessed using colony forming assay (CFA) (including RT112CP, a cisplatin-resistant variant of RT112). Expression was characterised by immunostaining a tissue microarray (TMA) representative of BCa grades and stages. Results: AIMP3 was constitutively expressed in the cell lines and was lower for T24 (high-grade) cells compared with RT4 (P < 0.01; two-tailed t-test). AIMP3 was expressed in normal urothelium and loss in BCa was related to grade and stage. AIMP3 localised to the nuclear compartment 1 h following irradiation and total expression increased after 72 h. Knockdown of AIMP3 increased clonogenic survival following irradiation (P < 0.04 in T24, RT112 and RT4). Targeting AIMP3 did not alter cisplatin sensitivity in RT112, but had a significant effect in RT112CP (P ¼ 0.01). Conclusion: We confirm loss of expression of the novel TSG, AIMP3, in BCa. AIMP3 migrates to the nucleus upon DNA damage and targeting the gene in vitro promotes cell survival and resistance to radiotherapy and chemotherapy.
Transperineal MRI-targeted Biopsy Versus Transperineal Template Prostate Mapping Biopsy in the Detection of Radio-recurrent Prostate Cancer A. Kanthabalan, M. Abl-Azzeez, M. Arya, A. Freeman, S. Punwani, H. Ahmed University College London Hospitals NHS Foundation Trust, London, UK
Introduction: External beam radiotherapy (EBRT) is effective in treating early localised prostate cancer. However, one third of men will experience biochemical failure by 5 years. Most men are expectantly managed with delayed hormones, yet half of these men have localised recurrence, which may be suitable for local salvage therapy. Multi-parametric magnetic resonance imaging (mpMRI) has shown high performance characteristics in detecting localised recurrence. We aimed to compare the cancer detection