Insulin sensitivity, cardiovascular function and bone health in women with early stage breast cancer before and after cancer treatment.

BACKGROUND: Cardiovascular disease is a leading cause of death in breast cancer survivors, but the underlying cause is not fully characterised. AIMS: To determine whether insulin sensitivity, cardiovascular risk markers and body composition were perturbed in women treated with chemotherapy for early stage breast cancer and whether perturbations occurred before or after cancer treatment. METHODS: Sixteen women with breast cancer and 17 control subjects were studied. Twelve breast cancer patients returned for a second visit following cancer treatment comprising chemotherapy (n = 2), or chemotherapy and radiotherapy (n = 10). The Matsuda index to estimate insulin sensitivity, fasting lipids, pulse wave velocity (PWV), reactive hyperaemia index (RHI) and body composition by dual energy X-ray absorptiometry were measured. RESULTS: There were no significant differences in age (53 ± 9 vs 54 ± 11 years; P = 0.82) or body mass index (28 ± 7 vs 28 ± 6; P = 0.97) between patients with breast cancer and controls. Patients with breast cancer had higher triglycerides than controls (1.2 ± 0.1 vs 0.8 ± 0.1 mmol/L; P = 0.03), but there were no significant differences in the Matsuda index, PWV and RHI. Following cancer treatment, there was a lower Matsuda index (6.3 ± 1.2 vs 5.2 ± 1.0; P = 0.01), but this was not associated with a significant change in vascular function. Bone mass fell by 3% from 2.27 ± 0.11 to 2.20 ± 0.10 kg after cancer treatment (P = 0.03). CONCLUSIONS: Patients with breast cancer had higher triglycerides before treatment and a reduction in insulin sensitivity and bone mass following cancer treatment. Future larger and longer-term studies should characterise the effect of reduced insulin sensitivity on rates of diabetes, cardiovascular disease, cancer outcomes and fracture. TRIAL REGISTRATION: ACTRN12614001055695.

Survival and late toxicities following concurrent chemo-radiotherapy for locally advanced stage III non-small cell lung cancer: findings of a 10-year Australian single centre experience with long term clinical follow up.

BACKGROUND: The preferred management of patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC) is concurrent chemo-radiotherapy (CRT). Acute CRT-related toxicities are well defined, however, less is known about late toxicities. The aim of the study was to examine the outcomes and late toxicities in Stage III NSCLC treated with CRT. METHODS: A retrospective review of the data from patients with stage III NSCLC treated with CRT was performed between May 2000 and June 2010. Demographics, tumour and treatment characteristics, toxicities and survival data were examined from hospital records of the patients. Progression free survival (PFS) and overall survival (OS) were evaluated by standard Kaplan-Meier survival curves. The censor date was set on 31 October 2016. RESULTS: Sixty-three patients were identified with a median age of 66.6 years [interquartile range (IQR) 57.2-72.1], two-third (n=41, 65.1%) were male, majority were current or ex-smokers (n=52, 82.5%), 42 (66.7%) patients had stage IIIB disease and 21 (33.3%) had stage IIIA disease. The most common histologic subtype was adenocarcinoma 30 (47.6%). The median PFS and OS of the whole population was 10.6 months (95% CI, 4.1-17.3 months) and 21 months (95% CI, 12.7-29.3 months) respectively. The 5-year OS rates for stage IIIA and IIIB were 24% and 16% respectively. The 1-, 3- and 5-year OS rates for all patients were 63.5%, 46% and 18.7% respectively. Acute grade 3 and 4 toxicities included 28 haematological and 17 non-haematological events. The incidence of late toxicities was 58.9%. Thirty-three events of late grade 3 and 4 toxicities were recorded. The most common late toxicity was symptomatic radiation-induced pulmonary fibrosis (39.3%), others include ototoxicity (7.1%), persistent dysphagia (7.1%) and one case of acute myeloid leukaemia. All patients that were alive at the censor date had developed radiation-induced fibrosis with associated symptoms of respiratory insufficiency. CONCLUSIONS: The 5-year OS of patients with stage III NSCLC treated with CRT was in keeping with survival figures reported from prospective clinical trials. There is, however, significant morbidity associated with long-term survival and this should be taken into account when making informed treatment decisions.

Late effects of oxaliplatin-induced peripheral neuropathy (LEON)--cross-sectional cohort study of patients with colorectal cancer surviving at least 2 years.

OBJECTIVES: Oxaliplatin accumulates in dorsal root ganglia, causing an axonal neuronopathy. Symptoms include numbness, pain and gait disturbance which may persist and impact on quality of life (QOL). Despite widespread use of this drug, its late effects and patient satisfaction outcomes have not been widely reported. Furthermore, there has been limited qualitative research published in this area. The objectives of this study were to establish the incidence and clinical impact of chronic peripheral neuropathy. METHODS: We conducted a cross-sectional observational study of patients who started oxaliplatin treatment at least 2 years prior to study commencement. Patients were assessed in three ways: clinical assessment encompassing neurological examination and nerve conduction studies to calculate a total neuropathy score (TNS); self-reported assessment via validated questionnaires; and assessment by recorded interview. The clinical and questionnaire-based assessments were analysed quantitatively and the interview data used for qualitative assessment. RESULTS: Twenty-five patients consented to participate. The mean starting dose of oxaliplatin given was 92 mg/m(2). The cumulative dose received ranged from 375 to 2,400 mg, with a mean cumulative dose of 1,515 mg. Oxaliplatin was ceased due to neuropathy in six patients (24 %), after a mean of 9 cycles of treatment. Modified TNS ranged from 1 to 15 with a mean of 9.5. There was a statistically significant correlation between cumulative oxaliplatin dose and TNS. Quality of life and functional impact questionnaires showed mildly lower physical quality of life, higher pain scores and functional impairment secondary to sensory deficit. Qualitative analysis demonstrated variable bio-psycho-social effects of chronic neuropathy but, importantly, highlighted that many patients felt they had been insufficiently warned of the risk of neuropathy. Despite this, the majority was satisfied with their decision to receive the drug. CONCLUSION: Many patients objectively demonstrated mild to moderate oxaliplatin neuropathy >2 years post-treatment. The majority of patients did not recall being warned of the risks of chronic peripheral neuropathy. Many of those who recall being warned did not feel sufficient emphasis was placed on the issue. Despite a varying burden of neuropathic symptoms, the majority of patients were highly satisfied with their decision to receive oxaliplatin.

Liver only metastatic disease in patients with metastatic colorectal cancer: impact of surgery and chemotherapy.

BACKGROUND: Metastatectomy in colorectal cancer (CRC) is now a standard of care with improved survival reported. Conversion chemotherapy has increased the population who are suitable for surgery. Here we assess patterns of care and treatment outcome in liver only metastases in South Australia using the clinical registry for advanced CRC. METHODS: We analysed the outcomes for patients with liver only metastatic involvement from the SA Metastatic CRC Database with the aim to investigate the role of chemotherapy on liver resection and outcome in comparison to liver resection only and chemotherapy without liver resection. Patients who had no therapy or non-surgical liver interventions were excluded for this analysis. RESULTS: One thousand nine hundred and eight patients were available for analysis, 687 (36%) had liver only metastatic disease and 455 (24%) had active therapy as defined. In total 54.2% (247/455) had chemotherapy alone, 19.1% (87/455) had liver resection alone, and 26.6% (121/455) had combined treatment. The three-year survival for chemotherapy, resection and combined treatment subgroups is 19.5%, 73.8% and 73.7%, respectively. The addition of chemotherapy to surgery did not improve survival. Switching chemotherapy was associated with a poorer outcome; three-year overall survival for chemotherapy switch was 62.5%, compared with same regimen pre- and post-74%, and chemo post-resection 80%. CONCLUSION: Liver only metastatic disease is common in CRC and patients undergoing liver resection have improved long-term survival. Survival for a combined approach of chemotherapy and hepatic resection is similar to surgery alone. Patients not suitable for surgery with liver only disease have a poorer prognosis highlighting the need for improved liver-directed therapies and attempts to covert non-resectable to resectable disease if possible.