Transforming the future of treatment for ovarian cancer

As for many other cancers, metastasis is the leading cause of death of patients with ovarian cancer. Vigorous basic and clinical research is being performed to initiate more efficacious treatment strategies to improve the poor outcome of women with this cancer. Current treatment for ovarian cancer includes advanced cyto-reductive surgery and traditional platinum and taxane combined chemotherapy. Clinical trials using novel cytotoxic reagents and tyrosine kinase inhibitors have also been progressing. In parallel, the application of robust unbiased high throughput research platforms using transcriptomic and proteomic approaches has identified that not only individual cell signalling pathways, but a network of molecular pathways, play an important role in the biology of ovarian cancer. Furthermore, intensive genomic and epigenetic analyses have also revealed single nucleotide polymorphisms associated with risk and/or aetiology of this cancer including patient response to treatment. Taken together, these approaches, that are advancing our understanding, will have an impact on the generation of new therapeutic approaches and strategies for improving the outcome and quality of life of patients with ovarian cancer in the near future.

Adverse breast cancer treatment effects: The economic case for making rehabilitative programs standard of care

Purpose: The purpose of this work was to evaluate the patient-borne financial cost of common, adverse breast cancer treatment-associated effects, comparing cost across women with or without these side-effects. Methods: 287 Australian women diagnosed with early-stage breast cancer were prospectively followed starting at six months post-surgery for 12 months, with three-monthly assessment of detailed treatment-related side effects and their direct and indirect patient costs attributable to breast cancer. Bootstrapping statistics were used to analyze cost data and adjusted logistic regression was used to evaluate the association between costs and adverse events from breast cancer. Costs were inflated and converted from 2002 Australian to 2014 US dollars. Results: More than 90% of women experienced at least one adverse effect (i.e. post-surgical issue, reaction to radiotherapy, upper-body symptoms or reduced function, lymphedema, fatigue or weight gain). On average, women paid $5,636 (95%CI: $4,694, $6,577) in total costs. Women with any one of the following symptoms (fatigue, reduced upper-body function, upper-body symptoms) or women who report ≥4 adverse treatment-related effects, have 1.5 to nearly 4 times the odds of having higher healthcare costs than women who do not report these complaints (p<0.05). Conclusions: Women face substantial economic burden due to a range of treatment-related health problems, which may persist beyond the treatment period. Improving breast cancer care by incorporating prospective surveillance of treatment-related side effects, and strategies for prevention and treatment of concerns (e.g., exercise) has real potential for reducing patient-borne costs.

Weight and weight change following breast cancer : evidence from a prospective, population-based, breast cancer cohort study

Background: While weight gain following breast cancer is considered common, results supporting these findings are dated. This work describes changes in body weight following breast cancer over 72 months, compares weight with normative data and explores whether weight changes over time are associated with personal, diagnostic, treatment or behavioral characteristics. Methods: A population-based sample of 287 Australian women diagnosed with early-stage invasive breast cancer was assessed prospectively at six, 12, 18 and 72 months post-surgery. Weight was clinically measured and linear mixed models were used to explore associations between weight and participant characteristics (collected via self-administered questionnaire). Those with BMI changes of one or more units were considered to have experienced clinically significant changes in weight. Results: More than half (57%) of participants were overweight or obese at 6 months post-surgery, and by 72 months post-surgery 68% of women were overweight or obese. Among those who gained more weight than age-matched norms, clinically significant weight gain between 6 and 18 months and 6 and 72 months post-surgery was observed in 24% and 39% of participants, respectively (median [range] weight gain: 3.9kg [2.0-11.3kg] and 5.2kg [0.6-28.7], respectively). Clinically-significant weight losses were observed in up to 24% of the sample (median [range] weight loss between 6 and 72 months post-surgery: -6.4kg [-1.9--24.6kg]). More extensive lymph node removal, being treated on the non-dominant side, receiving radiation therapy and lower physical activity levels at 6 months was associated with higher body weights post-breast cancer (group differences >3kg; all p<0.05). Conclusions: While average weight gain among breast cancer survivors in the long-term is small, subgroups of women experience greater gains linked with adverse health and above that experienced by age-matched counterparts. Weight change post-breast cancer is a contemporary public health issue and the integration of healthy weight education and support into standard breast cancer care has potential to significantly improve the length and quality of cancer survivorship.

The Lymphedema Evaluation in Gynecological cancer Study (LEGS): Design of a prospective, longitudinal, cohort study

Background The Lymphoedema Evaluation in Gynecological cancer Study (LEGS) was a longitudinal, observational, cohort study prospectively evaluating the incidence and risk factors of lower-limb lymphedema after treatment for gynecological cancer. Here we describe the study protocol and characteristics of the sample. Methods Women with a newly diagnosed gynecological cancer between June 1, 2008 and February 28, 2011, aged 18 years or older, and treated at one of six hospitals in Queensland, Australia, were eligible. Lymphedema was assessed by circumference measurements, bioimpedance spectroscopy, and self-reported swelling. LEGS incorporated a cohort of patients requiring surgery for benign gynecological conditions for comparison purposes. Data were collected prior to surgery and at regular intervals thereafter up to 2-years post-diagnosis. Results 546 women participated (408 cancer, 138 benign), with a 24-month retention rate of 78%. Clinical and treatment characteristics of participants were similar to the Queensland gynecological cancer population, except for a higher proportion of early-stage cervical cancers recruited to LEGS compared with Queensland proportions (89% versus 55%, respectively). Discussion Few imbalances were observed between participants with complete and incomplete follow-up data. The prospective design and collection of objective and patient-reported outcome data will allow comprehensive assessment of incidence and risk factors of lower-limb lymphedema.

The short-term impact of curative colorectal cancer treatment on physical activity, functional status and quality of life: A systematic review protocol

REVIEW QUESTION/OBJECTIVE The quantitative objectives are to identify the impact of curative colorectal cancer treatment (surgery or adjuvant therapy) on physical activity, functional status and quality of life within one year of treatment or diagnosis. INCLUSION CRITERIA Types of participants: This review will consider studies that include individuals aged 18 years and over who have been diagnosed with colorectal cancer. Types of intervention(s)/phenomena of interest: This review will consider studies that evaluate the impact of curative colorectal cancer treatment: surgery and/or adjuvant therapy. Types of outcomes: This review will consider studies that include the following outcome measures assessed within one year of diagnosis or treatment: Physical activity - any bodily movement produced by skeletal muscles resulting in energy expenditure. Physical activity is not exclusive to exercise; activities can also be walking, housework, occupational or leisure. Physical activity can be measured objectively using pedometers or accelerometers, or subjectively using self-reported measures. Functional status – measured as the capacity to perform all activities of daily living such as walking, showering, and eating; and instrumental activities of daily living such as (but not limited to) grocery shopping, housekeeping and laundry. Quality of life – defined as the individual meaning of mental, physical and psychosocial wellbeing, as measured by validated tools such as SF-36, EORTC-QLQ-C30, or FACT-C.

Lower preoperative quality of life increases postoperative risk of adverse events in women with endometrial cancer: results from the LACE trial

Objective: To examine the association between preoperative quality of life (QoL) and postoperative adverse events in women treated for endometrial cancer. Methods: 760 women with apparent Stage I endometrial cancer were randomised into a clinical trial evaluating laparoscopic versus open surgery. This analysis includes women with preoperative QoL measurements, from the Functional Assessment of Cancer Therapy- General (FACT-G) questionnaire, and who were followed up for at least 6 weeks after surgery (n=684). The outcomes for this study were defined as (1) the occurrence of moderate to severe AEs adverse events within 6 months (Common Toxicology Criteria (CTC) grade ≥3); and (2) any Serious Adverse Event (SAE). The association between preoperative QoL and the occurrence of AE was examined, after controlling for baseline comorbidity and other factors. Results: After adjusting for other factors, odds of occurrence of AE of CTC grade ≥3 were significantly increased with each unit decrease in baseline FACT-G score (OR=1.02, 95% CI 1.00-1.03, p=0.030), which was driven by physical well-being (PWB) (OR=1.09, 95% CI 1.04-1.13, p=0.0002) and functional well-being subscales (FWB) (OR=1.04, 95% CI 1.00-1.07, p=0.035). Similarly, odds of SAE occurrence were significantly increased with each unit decrease in baseline FACT-G score (OR=1.02, 95% CI 1.01-1.04, p=0.011), baseline PWB (OR=1.11, 95% CI 1.06-1.16, p<0.0001) or baseline FWB subscales (OR=1.05, 95% CI 1.01-1.10, p=0.0077). Conclusion: Women with early endometrial cancer presenting with lower QoL prior to surgery are at higher risk of developing a serious adverse event following surgery. Funding: Cancer Council Queensland, Cancer Council New South Wales, Cancer Council Victoria, Cancer Council, Western Australia; NHMRC project grant 456110; Cancer Australia project grant 631523; The Women and Infants Research Foundation, Western Australia; Royal Brisbane and Women’s Hospital Foundation; Wesley Research Institute; Gallipoli Research Foundation; Gynetech; TYCO Healthcare, Australia; Johnson and Johnson Medical, Australia; Hunter New England Centre for Gynaecological Cancer; Genesis Oncology Trust; and Smart Health Research Grant QLD Health.

Quality of life after early enteral feeding versus standard care for proven or suspected advanced epithelial ovarian cancer: Results from a randomised trial

Background Malnutrition is common in patients with advanced epithelial ovarian cancer (EOC), and is associated with impaired quality of life (QoL), longer hospital stay and higher risk of treatment-related adverse events. This phase III multi-centre randomised clinical trial tested early enteral feeding versus standard care on postoperative QoL. Methods From 2009 to 2013, 109 patients requiring surgery for suspected advanced EOC, moderately to severely malnourished were enrolled at five sites across Queensland and randomised to intervention (n = 53) or control (n = 56) groups. Intervention involved intraoperative nasojejunal tube placement and enteral feeding until adequate oral intake could be maintained. Despite being randomised to intervention, 20 patients did not receive feeds (13 did not receive the feeding tube; 7 had it removed early). Control involved postoperative diet as tolerated. QoL was measured at baseline, 6 weeks postoperatively and 30 days after the third cycle of chemotherapy. The primary outcome measure was the difference in QoL between the intervention and the control group. Secondary endpoints included treatment-related adverse event occurrence, length of stay, postoperative services use, and nutritional status. Results Baseline characteristics were comparable between treatment groups. No significant difference in QoL was found between the groups at any time point. There was a trend towards better nutritional status in patients who received the intervention but the differences did not reach statistical significance except for the intention-to-treat analysis at 7 days postoperatively (11.8 intervention vs. 13.8 control, p 0.04). Conclusion Early enteral feeding did not significantly improve patients' QoL compared to standard of care but may improve nutritional status.

No evidence for association of ataxia-telangiectasia mutated gene T2119C and C3161G amino acid substitution variants with risk of breast cancer

Background There is evidence that certain mutations in the double-strand break repair pathway ataxia-telangiectasia mutated gene act in a dominant-negative manner to increase the risk of breast cancer. There are also some reports to suggest that the amino acid substitution variants T2119C Ser707Pro and C3161G Pro1054Arg may be associated with breast cancer risk. We investigate the breast cancer risk associated with these two nonconservative amino acid substitution variants using a large Australian population-based case–control study. Methods The polymorphisms were genotyped in more than 1300 cases and 600 controls using 5' exonuclease assays. Case–control analyses and genotype distributions were compared by logistic regression. Results The 2119C variant was rare, occurring at frequencies of 1.4 and 1.3% in cases and controls, respectively (P = 0.8). There was no difference in genotype distribution between cases and controls (P = 0.8), and the TC genotype was not associated with increased risk of breast cancer (adjusted odds ratio = 1.08, 95% confidence interval = 0.59–1.97, P = 0.8). Similarly, the 3161G variant was no more common in cases than in controls (2.9% versus 2.2%, P = 0.2), there was no difference in genotype distribution between cases and controls (P = 0.1), and the CG genotype was not associated with an increased risk of breast cancer (adjusted odds ratio = 1.30, 95% confidence interval = 0.85–1.98, P = 0.2). This lack of evidence for an association persisted within groups defined by the family history of breast cancer or by age. Conclusion The 2119C and 3161G amino acid substitution variants are not associated with moderate or high risks of breast cancer in Australian women.