tAnGo is a large randomised trial assessing the addition of gemcitabine(G) to paclitaxel(T), foll... more tAnGo is a large randomised trial assessing the addition of gemcitabine(G) to paclitaxel(T), following epirubicin(E) and cyclophosphamide(C) in women with invasive higher risk early breast cancer. To assess the safety and tolerability of adding G, a detailed safety substudy was undertaken. A total of 135 patients had cardiac, pulmonary and hepatic function assessed at (i) randomisation, (ii) mid-chemotherapy, (iii) immediately post-chemotherapy and (iv) 6 months post-chemotherapy. Skin toxicity was assessed during radiotherapy. No differences were detected in FEV 1 or FVC levels between treatment arms or time points. Diffusion capacity (TL CO) reduced during treatment (Po0.0001), with a significantly lower drop in EC-GT patients (P ¼ 0.02). Most of the reduction occurred during EC and recovered by 6-months post treatment. There was no difference in cardiac function between treatment arms. Only 11 patients had echocardiography/MUGA results change from normal to abnormal during treatment, with only five having LVEFo50%. Transient transaminitis occurred in both treatment arms with significantly more in EC-GT patients postchemotherapy (AST P ¼ 0.03, ALT P ¼ 0.003), although the majority was low grade. There was no correlation between transaminitis and other toxicities. Both treatment regimens reported temporary reductions in pulmonary functions and transient transaminitis levels. Despite these being greater with EC-GT, both regimens appear well tolerated.
Background: The optimal duration of trastuzumab (T), when given together with chemotherapy and af... more Background: The optimal duration of trastuzumab (T), when given together with chemotherapy and after chemotherapy as adjuvant treatment in patients with HER2+ breast cancer (BC), is unknown. Whilst the international standard is 12 months of T, the benefits and harms of T treatment continued beyond the chemotherapy are unclear. Methods: Women with histologically confirmed node-negative or node-positive HER2+ BC were eligible for the trial (NCT00593697). The primary tumor diameter was required to be >5 mm in node-negative cancer. Patients with distant metastases, inflammatory cancer, clinically significant cardiac disease, left ventricular ejection fraction (LVEF) <50%, unknown estrogen receptor (ER) status, World Health Organization performance status >1, and those who had received neoadjuvant systemic cancer therapy were excluded. Patients were randomly assigned to 2 groups prior to starting systemic cancer therapy. The initial systemic treatment was identical in the groups consisting of 3 cycles of 3-weekly docetaxel plus T followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide (FE75C). Thereafter, no further T or chemotherapy was administered in Arm A, whereas in Arm B single-agent T was administered 3-weekly for 14 cycles to complete 1 year of T treatment. The docetaxel dose was either 80 mg/m2 or 100 mg/m2 (prespecified for each center). Radiation therapy and endocrine therapy (for patients with ER+ cancer) were given according to the institutional practice; the minimum scheduled duration of endocrine therapy was 5 years. The LVEF was measured pretreatment, and on study weeks 18, 31, 43, and 61 and month 36. The primary endpoint was disease-free survival (DFS) compared between the groups using a Cox model and the non-inferiority approach. Results: A total of 2,176 patients were entered into the study from 63 centers in 7 countries from Jan. 3, 2008 to Dec.16, 2014. The median follow-up time was 5.2 years at data collection closure (Dec. 31, 2016). The efficacy and safety data will be presented at the meeting. Citation Format: Joensuu H, Fraser J, Wildiers H, Huovinen R, Auvinen P, Utriainen M, Nyandoto P, Villman KK, Halonen P, Granstam-Björneklett H, Lundgren L, Yachnin J, Turpeenniemi-Hujanen T, Ritchie D, Huttunen T, Neven P, Canney P, Harvey VJ, Kellokumpu-Lehtinen P-L, Lindman H. A randomized phase III study of adjuvant trastuzumab for a duration of 9 weeks versus 1 year, combined with adjuvant taxane-anthracycline chemotherapy, for early HER2-positive breast cancer (the SOLD study) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS3-04.
BACKGROUND: Pre-clinical studies have demonstrated synergistic anti-tumour effects of chemotherap... more BACKGROUND: Pre-clinical studies have demonstrated synergistic anti-tumour effects of chemotherapy (CT) and zoledronic acid (ZOL). Within the AZURE trial, designed to determine whether the addition of ZOL to neoadjuvant therapy improves disease outcomes, a subgroup received neoadjuvant CT. We report a retrospective evaluation comparing pathological response in the primary tumour between treatment groups. METHODS: In total, 205 patients received neoadjuvant CT ± ZOL (CT þ ZOL, n ¼ 102; CT, n ¼ 103). The primary end point was pathologically assessed residual invasive tumour size (RITS) at surgery. Secondary end points were pathological complete response (pCR) rate and axillary nodal involvement. Following review of surgical pathology reports (n ¼ 195), outcome differences between groups were assessed adjusting for potential response modifiers. RESULTS: Baseline characteristics and CT treatments were similar. In multivariate analysis, allowing for biological and clinical factors known to influence tumour response, the adjusted mean RITS in CT and CT þ ZOL groups were 27.4 and 15.5 mm, respectively, giving a difference in means of 12 mm (95% confidence interval: 3.5-20.4 mm; P ¼ 0.006). The pCR rate was 6.9% in the CT group and 11.7% in the CT þ ZOL group (P ¼ 0.146). There was no difference in axillary nodal involvement (P ¼ 0.6315). CONCLUSION: These data suggest a possible direct anti-tumour effect of ZOL in combination with CT, warranting formal evaluation in prospective studies.
Background: The optimal duration of trastuzumab (T), when given together with chemotherapy and af... more Background: The optimal duration of trastuzumab (T), when given together with chemotherapy and after chemotherapy as adjuvant treatment in patients with HER2+ breast cancer (BC), is unknown. Whilst the international standard is 12 months of T, the benefits and harms of T treatment continued beyond the chemotherapy are unclear. Methods: Women with histologically confirmed node-negative or node-positive HER2+ BC were eligible for the trial (NCT00593697). The primary tumor diameter was required to be >5 mm in node-negative cancer. Patients with distant metastases, inflammatory cancer, clinically significant cardiac disease, left ventricular ejection fraction (LVEF) <50%, unknown estrogen receptor (ER) status, World Health Organization performance status >1, and those who had received neoadjuvant systemic cancer therapy were excluded. Patients were randomly assigned to 2 groups prior to starting systemic cancer therapy. The initial systemic treatment was identical in the groups...
Radiation induced angiosarcomas (RIA) can affect breast cancer patients who had radiotherapy foll... more Radiation induced angiosarcomas (RIA) can affect breast cancer patients who had radiotherapy following conservative breast surgery. They are very rare tumors and often their diagnosis is delayed due to their benign appearance and difficulty in differentiation from radiation induced skin changes. Therefore it is very important that clinicians are aware of their existence. We report here a case of RIA followed by discussion and review of literature.
Adjuvant bisphosphonates improve disease outcomes in postmenopausal early breast cancer (EBC) but... more Adjuvant bisphosphonates improve disease outcomes in postmenopausal early breast cancer (EBC) but the long-term effects are poorly described. The AZURE trial (ISRCTN79831382) was designed to determine whether adjuvant zoledronic acid (ZOL) improves disease outcomes in EBC. Previous analyses showed no effect on overall outcomes but identified benefits in postmenopausal women. Here we present the long-term risks and benefits of adjuvant ZOL with 10-years follow-up. Patients and methods: 3360 patients with stage II/III breast cancer were included in an academic, international, phase III, randomized, open label trial. Patients were followed up on a regular schedule until 10 years. Patients were randomized on a 1:1 basis to standard adjuvant systemic therapy +/− intravenous ZOL 4 mg every 3-4 weeks x6, and then at reduced frequency to complete 5 years treatment. The primary outcome was disease free survival (DFS). Secondary outcomes included invasive DFS (IDFS), overall survival (OS), sites of recurrence, skeletal morbidity and treatment outcomes according to primary tumor amplification of the transcription factor, MAF. Pre-planned subgroup analyses focused on interactions between menopausal status and treatment effects. Results: With a median follow up of 117 months [IQR 70.4-120.4), DFS and IDFS were similar in both arms (HR DFS = 0.94, 95%CI = 0.84-1.06, p = 0.340; HR IDFS = 0.91, 95%CI = 0.82-1.02, p = 0.116). However, outcomes remain improved with ZOL in postmenopausal women (HR DFS = 0.82, 95%CI = 0.67-1.00; HR IDFS = 0.78, 95%CI = 0.64-0.94). In the 79% of tested women with a MAF FISH negative tumor, ZOL improved IDFS (HR IDFS = 0.75, 95%CI = 0.58-0.97) and OS HR OS = 0.69, 95%CI = 0.50-0.94), irrespective of menopause. ZOL did not improve disease outcomes in MAF FISH + tumors. Bone metastases as a first DFS recurrence (B DFS) were reduced with ZOL (HR B-DFS = 0.76, 95%CI = 0.63-0.92, p = 0.005). ZOL reduced skeletal morbidity with fewer fractures and skeletal events after disease recurrence. 30 cases of osteonecrosis of the jaw in the ZOL arm (1.8%) have occurred.
Clinical Hemorheology and Microcirculation, Dec 22, 2016
The filtration of dilute erythrocyte suspension over 5 micron polycarbonate filters was examined ... more The filtration of dilute erythrocyte suspension over 5 micron polycarbonate filters was examined as a measure of erythrocyte deformability in 20 insulin requiring diabetic patients and related to glycaemic control as assessed by fasting whole blood glucose and HbAlc. Twelve patients were
The aims of the studies were to examine blood rheology, haemostatic factors and peripheral blood ... more The aims of the studies were to examine blood rheology, haemostatic factors and peripheral blood flow in diabetes mellitus in relation to treatment and the presence of vascular damage. First, studies of the specificity of positive pressure filtration of dilute erythrocyte suspensions as a measure of erythrocyte deformability were made. Second, the effects of improved blood glucose control (achieved by outpatient management) on whole blood viscosity, haemostatic factors, peripheral blood flow and peripheral nerve function was examined. Third, a double-blind crossover study of the effects of treatment with biosynthetic human insulin (BHI) and purified porcine insulin (PPI) on blood rheology, haemostatic factors and peripheral blood flow was carried out.
Objectives To determine functional and psychological benefits of a 12 week supervised group exerc... more Objectives To determine functional and psychological benefits of a 12 week supervised group exercise programme during treatment for early stage breast cancer, with six month follow-up. Design Pragmatic randomised controlled prospective open trial. Setting Three National Health Service oncology clinics in Scotland and community exercise facilities. Participants 203 women entered the study; 177 completed the six month follow-up. Interventions Supervised 12 week group exercise programme in addition to usual care, compared with usual care. Main outcome measures Functional assessment of cancer therapy (FACT) questionnaire, Beck depression inventory, positive and negative affect scale, body mass index, seven day recall of physical activity, 12 minute walk test, and assessment of shoulder mobility. ResultsMixed effects models with adjustment for baseline values, study site, treatment at baseline, and age gave intervention effect estimates (intervention minus control) at 12 weeks of 129 (95...
Breast cancer is the second-leading cause of cancer death among women after lung cancer. There wi... more Breast cancer is the second-leading cause of cancer death among women after lung cancer. There will be an estimated 46,000 new cases of breast cancer in the UK in 2010 and an estimated 12,000 women are predicted to die from the disease. The prognosis for patients with breast cancer has improved in recent years due to early detection through mammographic screening and refinement of adjuvant therapies. Around 90% of women diagnosed with stage I breast cancer survive beyond five years and the five-year survival rate for all patients (diagnosed 2001–2003, England & Wales) was 80%.
In October 2016 a team comprising three Radiation Oncologists and one Medical Physicist made a vi... more In October 2016 a team comprising three Radiation Oncologists and one Medical Physicist made a visit to Kathmandu, Nepal. The purpose of the visit was to deliver a Radiotherapy Treatment Planning course to trainees, Consultant Radiation Oncologists and Physicists. Visits were made to three radiotherapy centres in Kathmandu: Bir Hospital Kathmandu (1 Co60), Kathmandu Cancer Centre(1 linac) and the Nepal Cancer Centre (1 linac). This paper provides a snapshot of the challenges facing the delivery of Radiotherapy services in Nepal. There is a shortage of trained Medical Physicists. Each of the centres visited has only one Physicist for all treatment planning and machine related activities. The staff are enthusiastic, eager to learn and, like physicists worldwide, aspire to deliver high quality treatment using the latest technologies. However, the lack of support in both human and material resources presents significant challenges to delivering safe and timely radiotherapy. This results...
Purpose: This study aimed to evaluate the outcomes of juxtapapillary choroidal melanomas treated ... more Purpose: This study aimed to evaluate the outcomes of juxtapapillary choroidal melanomas treated with notched ruthenium-106 plaques. Methods: Juxtapapillary choroidal melanomas (tumours within 2 disc diameters from the optic disc) treated with notched ruthenium-106 plaques (Eckert & Ziegler, BEBIG, Berlin, Germany) at the Scottish Ocular Oncology Service between 2009 and 2015 were retrospectively reviewed. The data were analysed with respect to various outcome measures including recurrence, complications, vision, and eye preservation. Results: We reviewed 40 patients with a median tumour diameter of 8.4 mm (range 5–17 mm) and a median thickness of 2.5 mm (range 1.1–6 mm). AJCC tumour category distribution was 62.5% T1, 32.5% T2, and 5% T3 tumours. The mean presenting vision was 0.3 logMAR, and the mean final vision was 0.7 logMAR, with 62.5% retaining >1.0 logMAR and 50% retaining >0.3 logMAR at the final follow-up. The median follow-up was 51 months (14–100 months). Over the ...
1015 Background: Neo-tAnGo was an NCRI UK neoadjuvant breast cancer study testing the addition of... more 1015 Background: Neo-tAnGo was an NCRI UK neoadjuvant breast cancer study testing the addition of gemcitabine to anthracycline and taxane-based treatment and also the sequencing of chemotherapy. In a translational substudy, sequential fresh tissue was analysed for PAM 50 subgroups. Methods: Neo-tAnGo recruited 831 patients. 162 patients were consented for Neo-tAnGo Science, for 3 additional fresh tissue samples to be taken at diagnosis (diag), mid-chemotherapy (CT) and end-CT. Standard methodology was used for PAM 50 subtyping. Results: Fresh tissue samples at diag were received from 123 patients (pts). 45 pts (37%) had 2 additional samples provided (at mid- and end-CT). 57 pts (46%) had 1 additional sample provided (34 at mid-CT, 23 at end-CT). PAM 50 subtyping at diag was as follows: 31 (25%) BASAL; 30 (24%) HER2; 39 (32%) LUM B; 13 (11%) LUM A; 10 (8%) NORMAL-like. Pathological complete response rates (pCR: no disease in breast or axillary nodes, n = 121 pts) differed between PAM...
Background: The optimal sequence of adjuvant chemotherapy and radiotherapy for breast cancer is u... more Background: The optimal sequence of adjuvant chemotherapy and radiotherapy for breast cancer is unknown. SECRAB assesses whether local control can be improved without increased toxicity. Methods: SECRAB was a prospective, open-label, multi-centre, phase III trial comparing synchronous to sequential chemo-radiotherapy, conducted in 48 UK centres. Patients with invasive, early stage breast cancer were eligible. Randomisation (performed using random permuted block assignment) was stratified by centre, axillary surgery, chemotherapy, and radiotherapy boost. Permitted chemotherapy regimens included CMF and anthracycline-CMF. Synchronous radiotherapy was administered between cycles two and three for CMF or five and six for anthracycline-CMF. Sequential radiotherapy was delivered on chemotherapy completion. Radiotherapy schedules included 40 Gy/15F over three weeks, and 50 Gy/25F over five weeks. The primary outcome was local recurrence at five and ten years, defined as time to local recurrence, and analysed by intention to treat. ClinicalTrials.gov NCT00003893. Findings: Between 02-July-1998 and 25-March-2004, 2297 patients were recruited (1150 synchronous and 1146 sequential). Baseline characteristics were balanced. With 10.2 years median follow-up, the ten-year local recurrence rates were 4.6% and 7.1% in the synchronous and sequential arms respectively (hazard ratio (HR) 0.62; 95% confidence interval (CI): 0.43-0.90; p = 0.012). In a planned subgroup analysis of anthracycline-CMF, the ten-year local recurrence rates difference were 3.5% versus 6.7% respectively (HR 0.48 95% CI: 0.26-0.88; p = 0.018). There was no significant difference in overall or disease-free survival. 24% of patients on the synchronous arm suffered moderate/severe acute skin reactions compared to 15% on the sequential arm (p < 0.0001). There were no significant differences in late adverse effects apart from telangiectasia (p = 0.03). Interpretation: Synchronous chemo-radiotherapy significantly improved local recurrence rates. This was delivered with an acceptable increase in acute toxicity. The greatest benefit of synchronous chemoradiation was in patients treated with anthracycline-CMF.
tAnGo is a large randomised trial assessing the addition of gemcitabine(G) to paclitaxel(T), foll... more tAnGo is a large randomised trial assessing the addition of gemcitabine(G) to paclitaxel(T), following epirubicin(E) and cyclophosphamide(C) in women with invasive higher risk early breast cancer. To assess the safety and tolerability of adding G, a detailed safety substudy was undertaken. A total of 135 patients had cardiac, pulmonary and hepatic function assessed at (i) randomisation, (ii) mid-chemotherapy, (iii) immediately post-chemotherapy and (iv) 6 months post-chemotherapy. Skin toxicity was assessed during radiotherapy. No differences were detected in FEV 1 or FVC levels between treatment arms or time points. Diffusion capacity (TL CO) reduced during treatment (Po0.0001), with a significantly lower drop in EC-GT patients (P ¼ 0.02). Most of the reduction occurred during EC and recovered by 6-months post treatment. There was no difference in cardiac function between treatment arms. Only 11 patients had echocardiography/MUGA results change from normal to abnormal during treatment, with only five having LVEFo50%. Transient transaminitis occurred in both treatment arms with significantly more in EC-GT patients postchemotherapy (AST P ¼ 0.03, ALT P ¼ 0.003), although the majority was low grade. There was no correlation between transaminitis and other toxicities. Both treatment regimens reported temporary reductions in pulmonary functions and transient transaminitis levels. Despite these being greater with EC-GT, both regimens appear well tolerated.
Background: The optimal duration of trastuzumab (T), when given together with chemotherapy and af... more Background: The optimal duration of trastuzumab (T), when given together with chemotherapy and after chemotherapy as adjuvant treatment in patients with HER2+ breast cancer (BC), is unknown. Whilst the international standard is 12 months of T, the benefits and harms of T treatment continued beyond the chemotherapy are unclear. Methods: Women with histologically confirmed node-negative or node-positive HER2+ BC were eligible for the trial (NCT00593697). The primary tumor diameter was required to be &gt;5 mm in node-negative cancer. Patients with distant metastases, inflammatory cancer, clinically significant cardiac disease, left ventricular ejection fraction (LVEF) &lt;50%, unknown estrogen receptor (ER) status, World Health Organization performance status &gt;1, and those who had received neoadjuvant systemic cancer therapy were excluded. Patients were randomly assigned to 2 groups prior to starting systemic cancer therapy. The initial systemic treatment was identical in the groups consisting of 3 cycles of 3-weekly docetaxel plus T followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide (FE75C). Thereafter, no further T or chemotherapy was administered in Arm A, whereas in Arm B single-agent T was administered 3-weekly for 14 cycles to complete 1 year of T treatment. The docetaxel dose was either 80 mg/m2 or 100 mg/m2 (prespecified for each center). Radiation therapy and endocrine therapy (for patients with ER+ cancer) were given according to the institutional practice; the minimum scheduled duration of endocrine therapy was 5 years. The LVEF was measured pretreatment, and on study weeks 18, 31, 43, and 61 and month 36. The primary endpoint was disease-free survival (DFS) compared between the groups using a Cox model and the non-inferiority approach. Results: A total of 2,176 patients were entered into the study from 63 centers in 7 countries from Jan. 3, 2008 to Dec.16, 2014. The median follow-up time was 5.2 years at data collection closure (Dec. 31, 2016). The efficacy and safety data will be presented at the meeting. Citation Format: Joensuu H, Fraser J, Wildiers H, Huovinen R, Auvinen P, Utriainen M, Nyandoto P, Villman KK, Halonen P, Granstam-Björneklett H, Lundgren L, Yachnin J, Turpeenniemi-Hujanen T, Ritchie D, Huttunen T, Neven P, Canney P, Harvey VJ, Kellokumpu-Lehtinen P-L, Lindman H. A randomized phase III study of adjuvant trastuzumab for a duration of 9 weeks versus 1 year, combined with adjuvant taxane-anthracycline chemotherapy, for early HER2-positive breast cancer (the SOLD study) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS3-04.
BACKGROUND: Pre-clinical studies have demonstrated synergistic anti-tumour effects of chemotherap... more BACKGROUND: Pre-clinical studies have demonstrated synergistic anti-tumour effects of chemotherapy (CT) and zoledronic acid (ZOL). Within the AZURE trial, designed to determine whether the addition of ZOL to neoadjuvant therapy improves disease outcomes, a subgroup received neoadjuvant CT. We report a retrospective evaluation comparing pathological response in the primary tumour between treatment groups. METHODS: In total, 205 patients received neoadjuvant CT ± ZOL (CT þ ZOL, n ¼ 102; CT, n ¼ 103). The primary end point was pathologically assessed residual invasive tumour size (RITS) at surgery. Secondary end points were pathological complete response (pCR) rate and axillary nodal involvement. Following review of surgical pathology reports (n ¼ 195), outcome differences between groups were assessed adjusting for potential response modifiers. RESULTS: Baseline characteristics and CT treatments were similar. In multivariate analysis, allowing for biological and clinical factors known to influence tumour response, the adjusted mean RITS in CT and CT þ ZOL groups were 27.4 and 15.5 mm, respectively, giving a difference in means of 12 mm (95% confidence interval: 3.5-20.4 mm; P ¼ 0.006). The pCR rate was 6.9% in the CT group and 11.7% in the CT þ ZOL group (P ¼ 0.146). There was no difference in axillary nodal involvement (P ¼ 0.6315). CONCLUSION: These data suggest a possible direct anti-tumour effect of ZOL in combination with CT, warranting formal evaluation in prospective studies.
Background: The optimal duration of trastuzumab (T), when given together with chemotherapy and af... more Background: The optimal duration of trastuzumab (T), when given together with chemotherapy and after chemotherapy as adjuvant treatment in patients with HER2+ breast cancer (BC), is unknown. Whilst the international standard is 12 months of T, the benefits and harms of T treatment continued beyond the chemotherapy are unclear. Methods: Women with histologically confirmed node-negative or node-positive HER2+ BC were eligible for the trial (NCT00593697). The primary tumor diameter was required to be >5 mm in node-negative cancer. Patients with distant metastases, inflammatory cancer, clinically significant cardiac disease, left ventricular ejection fraction (LVEF) <50%, unknown estrogen receptor (ER) status, World Health Organization performance status >1, and those who had received neoadjuvant systemic cancer therapy were excluded. Patients were randomly assigned to 2 groups prior to starting systemic cancer therapy. The initial systemic treatment was identical in the groups...
Radiation induced angiosarcomas (RIA) can affect breast cancer patients who had radiotherapy foll... more Radiation induced angiosarcomas (RIA) can affect breast cancer patients who had radiotherapy following conservative breast surgery. They are very rare tumors and often their diagnosis is delayed due to their benign appearance and difficulty in differentiation from radiation induced skin changes. Therefore it is very important that clinicians are aware of their existence. We report here a case of RIA followed by discussion and review of literature.
Adjuvant bisphosphonates improve disease outcomes in postmenopausal early breast cancer (EBC) but... more Adjuvant bisphosphonates improve disease outcomes in postmenopausal early breast cancer (EBC) but the long-term effects are poorly described. The AZURE trial (ISRCTN79831382) was designed to determine whether adjuvant zoledronic acid (ZOL) improves disease outcomes in EBC. Previous analyses showed no effect on overall outcomes but identified benefits in postmenopausal women. Here we present the long-term risks and benefits of adjuvant ZOL with 10-years follow-up. Patients and methods: 3360 patients with stage II/III breast cancer were included in an academic, international, phase III, randomized, open label trial. Patients were followed up on a regular schedule until 10 years. Patients were randomized on a 1:1 basis to standard adjuvant systemic therapy +/− intravenous ZOL 4 mg every 3-4 weeks x6, and then at reduced frequency to complete 5 years treatment. The primary outcome was disease free survival (DFS). Secondary outcomes included invasive DFS (IDFS), overall survival (OS), sites of recurrence, skeletal morbidity and treatment outcomes according to primary tumor amplification of the transcription factor, MAF. Pre-planned subgroup analyses focused on interactions between menopausal status and treatment effects. Results: With a median follow up of 117 months [IQR 70.4-120.4), DFS and IDFS were similar in both arms (HR DFS = 0.94, 95%CI = 0.84-1.06, p = 0.340; HR IDFS = 0.91, 95%CI = 0.82-1.02, p = 0.116). However, outcomes remain improved with ZOL in postmenopausal women (HR DFS = 0.82, 95%CI = 0.67-1.00; HR IDFS = 0.78, 95%CI = 0.64-0.94). In the 79% of tested women with a MAF FISH negative tumor, ZOL improved IDFS (HR IDFS = 0.75, 95%CI = 0.58-0.97) and OS HR OS = 0.69, 95%CI = 0.50-0.94), irrespective of menopause. ZOL did not improve disease outcomes in MAF FISH + tumors. Bone metastases as a first DFS recurrence (B DFS) were reduced with ZOL (HR B-DFS = 0.76, 95%CI = 0.63-0.92, p = 0.005). ZOL reduced skeletal morbidity with fewer fractures and skeletal events after disease recurrence. 30 cases of osteonecrosis of the jaw in the ZOL arm (1.8%) have occurred.
Clinical Hemorheology and Microcirculation, Dec 22, 2016
The filtration of dilute erythrocyte suspension over 5 micron polycarbonate filters was examined ... more The filtration of dilute erythrocyte suspension over 5 micron polycarbonate filters was examined as a measure of erythrocyte deformability in 20 insulin requiring diabetic patients and related to glycaemic control as assessed by fasting whole blood glucose and HbAlc. Twelve patients were
The aims of the studies were to examine blood rheology, haemostatic factors and peripheral blood ... more The aims of the studies were to examine blood rheology, haemostatic factors and peripheral blood flow in diabetes mellitus in relation to treatment and the presence of vascular damage. First, studies of the specificity of positive pressure filtration of dilute erythrocyte suspensions as a measure of erythrocyte deformability were made. Second, the effects of improved blood glucose control (achieved by outpatient management) on whole blood viscosity, haemostatic factors, peripheral blood flow and peripheral nerve function was examined. Third, a double-blind crossover study of the effects of treatment with biosynthetic human insulin (BHI) and purified porcine insulin (PPI) on blood rheology, haemostatic factors and peripheral blood flow was carried out.
Objectives To determine functional and psychological benefits of a 12 week supervised group exerc... more Objectives To determine functional and psychological benefits of a 12 week supervised group exercise programme during treatment for early stage breast cancer, with six month follow-up. Design Pragmatic randomised controlled prospective open trial. Setting Three National Health Service oncology clinics in Scotland and community exercise facilities. Participants 203 women entered the study; 177 completed the six month follow-up. Interventions Supervised 12 week group exercise programme in addition to usual care, compared with usual care. Main outcome measures Functional assessment of cancer therapy (FACT) questionnaire, Beck depression inventory, positive and negative affect scale, body mass index, seven day recall of physical activity, 12 minute walk test, and assessment of shoulder mobility. ResultsMixed effects models with adjustment for baseline values, study site, treatment at baseline, and age gave intervention effect estimates (intervention minus control) at 12 weeks of 129 (95...
Breast cancer is the second-leading cause of cancer death among women after lung cancer. There wi... more Breast cancer is the second-leading cause of cancer death among women after lung cancer. There will be an estimated 46,000 new cases of breast cancer in the UK in 2010 and an estimated 12,000 women are predicted to die from the disease. The prognosis for patients with breast cancer has improved in recent years due to early detection through mammographic screening and refinement of adjuvant therapies. Around 90% of women diagnosed with stage I breast cancer survive beyond five years and the five-year survival rate for all patients (diagnosed 2001–2003, England & Wales) was 80%.
In October 2016 a team comprising three Radiation Oncologists and one Medical Physicist made a vi... more In October 2016 a team comprising three Radiation Oncologists and one Medical Physicist made a visit to Kathmandu, Nepal. The purpose of the visit was to deliver a Radiotherapy Treatment Planning course to trainees, Consultant Radiation Oncologists and Physicists. Visits were made to three radiotherapy centres in Kathmandu: Bir Hospital Kathmandu (1 Co60), Kathmandu Cancer Centre(1 linac) and the Nepal Cancer Centre (1 linac). This paper provides a snapshot of the challenges facing the delivery of Radiotherapy services in Nepal. There is a shortage of trained Medical Physicists. Each of the centres visited has only one Physicist for all treatment planning and machine related activities. The staff are enthusiastic, eager to learn and, like physicists worldwide, aspire to deliver high quality treatment using the latest technologies. However, the lack of support in both human and material resources presents significant challenges to delivering safe and timely radiotherapy. This results...
Purpose: This study aimed to evaluate the outcomes of juxtapapillary choroidal melanomas treated ... more Purpose: This study aimed to evaluate the outcomes of juxtapapillary choroidal melanomas treated with notched ruthenium-106 plaques. Methods: Juxtapapillary choroidal melanomas (tumours within 2 disc diameters from the optic disc) treated with notched ruthenium-106 plaques (Eckert & Ziegler, BEBIG, Berlin, Germany) at the Scottish Ocular Oncology Service between 2009 and 2015 were retrospectively reviewed. The data were analysed with respect to various outcome measures including recurrence, complications, vision, and eye preservation. Results: We reviewed 40 patients with a median tumour diameter of 8.4 mm (range 5–17 mm) and a median thickness of 2.5 mm (range 1.1–6 mm). AJCC tumour category distribution was 62.5% T1, 32.5% T2, and 5% T3 tumours. The mean presenting vision was 0.3 logMAR, and the mean final vision was 0.7 logMAR, with 62.5% retaining >1.0 logMAR and 50% retaining >0.3 logMAR at the final follow-up. The median follow-up was 51 months (14–100 months). Over the ...
1015 Background: Neo-tAnGo was an NCRI UK neoadjuvant breast cancer study testing the addition of... more 1015 Background: Neo-tAnGo was an NCRI UK neoadjuvant breast cancer study testing the addition of gemcitabine to anthracycline and taxane-based treatment and also the sequencing of chemotherapy. In a translational substudy, sequential fresh tissue was analysed for PAM 50 subgroups. Methods: Neo-tAnGo recruited 831 patients. 162 patients were consented for Neo-tAnGo Science, for 3 additional fresh tissue samples to be taken at diagnosis (diag), mid-chemotherapy (CT) and end-CT. Standard methodology was used for PAM 50 subtyping. Results: Fresh tissue samples at diag were received from 123 patients (pts). 45 pts (37%) had 2 additional samples provided (at mid- and end-CT). 57 pts (46%) had 1 additional sample provided (34 at mid-CT, 23 at end-CT). PAM 50 subtyping at diag was as follows: 31 (25%) BASAL; 30 (24%) HER2; 39 (32%) LUM B; 13 (11%) LUM A; 10 (8%) NORMAL-like. Pathological complete response rates (pCR: no disease in breast or axillary nodes, n = 121 pts) differed between PAM...
Background: The optimal sequence of adjuvant chemotherapy and radiotherapy for breast cancer is u... more Background: The optimal sequence of adjuvant chemotherapy and radiotherapy for breast cancer is unknown. SECRAB assesses whether local control can be improved without increased toxicity. Methods: SECRAB was a prospective, open-label, multi-centre, phase III trial comparing synchronous to sequential chemo-radiotherapy, conducted in 48 UK centres. Patients with invasive, early stage breast cancer were eligible. Randomisation (performed using random permuted block assignment) was stratified by centre, axillary surgery, chemotherapy, and radiotherapy boost. Permitted chemotherapy regimens included CMF and anthracycline-CMF. Synchronous radiotherapy was administered between cycles two and three for CMF or five and six for anthracycline-CMF. Sequential radiotherapy was delivered on chemotherapy completion. Radiotherapy schedules included 40 Gy/15F over three weeks, and 50 Gy/25F over five weeks. The primary outcome was local recurrence at five and ten years, defined as time to local recurrence, and analysed by intention to treat. ClinicalTrials.gov NCT00003893. Findings: Between 02-July-1998 and 25-March-2004, 2297 patients were recruited (1150 synchronous and 1146 sequential). Baseline characteristics were balanced. With 10.2 years median follow-up, the ten-year local recurrence rates were 4.6% and 7.1% in the synchronous and sequential arms respectively (hazard ratio (HR) 0.62; 95% confidence interval (CI): 0.43-0.90; p = 0.012). In a planned subgroup analysis of anthracycline-CMF, the ten-year local recurrence rates difference were 3.5% versus 6.7% respectively (HR 0.48 95% CI: 0.26-0.88; p = 0.018). There was no significant difference in overall or disease-free survival. 24% of patients on the synchronous arm suffered moderate/severe acute skin reactions compared to 15% on the sequential arm (p < 0.0001). There were no significant differences in late adverse effects apart from telangiectasia (p = 0.03). Interpretation: Synchronous chemo-radiotherapy significantly improved local recurrence rates. This was delivered with an acceptable increase in acute toxicity. The greatest benefit of synchronous chemoradiation was in patients treated with anthracycline-CMF.
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