Quality of life after total laparoscopic hysterectomy versus total abdominal hysterectomy for stage I endometrial cancer (LACE) : a randomised trial

Background: The two-stage Total Laparoscopic Hysterectomy (TLH) versus Total Abdominal Hysterectomy (TAH) for stage I endometrial cancer (LACE) randomised controlled trial was initiated in 2005. The primary objective of stage 1 was to assess whether TLH results in equivalent or improved QoL up to 6 months after surgery compared to TAH. The primary objective of stage 2 was to test the hypothesis that disease-free survival at 4.5 years is equivalent for TLH and TAH. Results addressing the primary objective of stage 1 of the LACE trial are presented here. Methods: The first 361 LACE participants (TAH n= 142, TLH n=190) were enrolled in the QoL substudy at 19 centres across Australia, New Zealand and Hong Kong, and 332 completed the QoL analysis. Randomisation was performed centrally and independently from other study procedures via a computer generated, web-based system (providing concealment of the next assigned treatment) using stratified permuted blocks of 3 and 6, and assigned patients with histologically confirmed stage 1 endometrioid endometrial adenocarcinoma and ECOG performance status <2 to TLH or TAH stratified by histological grade and study centre. No blinding of patients or study personnel was attempted. QoL was measured at baseline, 1 and 4 weeks (early), and 3 and 6 months (late) after surgery using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. The primary endpoint was the difference between the groups in QoL change from baseline at early and late time points (a 5% difference was considered clinically significant). Analysis was performed according to the intention-to-treat principle using generalized estimating equations on differences from baseline for the early and late QoL recovery. The LACE trial is registered with clinicaltrials.gov (NCT00096408) and the Australian New Zealand Clinical Trials Registry (CTRN12606000261516). Patients for both stages of the trial have now been recruited and are being followed up for disease-specific outcomes. Findings: The proportion of missing values at the 5%, 10% 15% and 20% differences in the FACT-G scale was 6% (12/190) in the TLH and 14% (20/142) in the TAH group. There were 8/332 conversions (2.4%, 7 of which were from TLH to TAH). In the early phase of recovery, patients undergoing TLH reported significantly greater improvement of QoL from baseline compared to TAH in all subscales except the emotional and social well-being subscales. Improvements in QoL up to 6 months post-surgery continued to favour TLH except for the emotional and social well-being of the FACT and the visual analogue scale of the EuroQoL five dimensions (EuroQoL-VAS). Length of operating time was significantly longer in the TLH group (138±43 mins), than in the TAH group at (109±34 mins; p=0.001). While the proportion of intraoperative adverse events was similar between the treatment groups (TAH 8/142, 5.6%; TLH 14/190, 7.4%; p=0.55), postoperatively, twice as many patients in the TAH group experienced adverse events of CTC grade 3+ than in the TLH group (33/142, 23.2% and 22/190, 11.6%, respectively; p=0.004). Postoperative serious adverse events occurred more frequently in patients who had a TAH (27/142, 19.0%) than a TLH (15/190, 7.9%) (p=0.002). Interpretation: QoL improvements from baseline during early and later phases of recovery, and the adverse event profile significantly favour TLH compared to TAH for patients treated for Stage I endometrial cancer.

Upper-body morbidity following breast cancer treatment is common, may persist longer-term and adversely influences quality of life

Background: Impairments in upper-body function (UBF) are common following breast cancer. However, the relationship between arm morbidity and quality of life (QoL) remains unclear. This investigation uses longitudinal data to describe UBF in a population-based sample of women with breast cancer and examines its relationship with QoL. ---------- Methods: Australian women (n = 287) with unilateral breast cancer were assessed at three-monthly intervals, from six- to 18-months post-surgery (PS). Strength, endurance and flexibility were used to assess objective UBF, while the Disability of the Arm, Shoulder and Hand questionnaire and the Functional Assessment of Cancer Therapy- Breast questionnaire were used to assess self-reported UBF and QoL, respectively. ---------- Results: Although mean UBF improved over time, up to 41% of women revealed declines in UBF between sixand 18-months PS. Older age, lower socioeconomic position, treatment on the dominant side, mastectomy, more extensive lymph node removal and having lymphoedema each increased odds of declines in UBF by at least twofold (p < 0.05). Lower baseline and declines in perceived UBF between six- and 18-months PS were each associated with poorer QoL at 18-months PS (p < 0.05). ---------- Conclusions: Significant upper-body morbidity is experienced by many following breast cancer treatment, persisting longer term, and adversely influencing the QoL of breast cancer survivors.

Lifestyle factors associated concurrently and prospectively with co-morbid cardiovascular disease in a population-based cohort of colorectal cancer survivors

Aims To assess self-reported lifetime prevalence of cardiovascular disease (CVD) among colorectal cancer survivors, and examine the cross-sectional and prospective associations of lifestyle factors with co-morbid CVD. Methods Colorectal cancer survivors were recruited (n = 1966). Data were collected at approximately 5, 12, 24 and 36 months post-diagnosis. Cross-sectional findings included six CVD categories (hypercholesterolaemia, hypertension, diabetes, heart failure, kidney disease and ischaemic heart disease (IHD)) at 5 months post-diagnosis. Longitudinal outcomes included the probability of developing (de novo) co-morbid CVD by 36 months post-diagnosis. Lifestyle factors included body mass index, physical activity, television (TV) viewing, alcohol consumption and smoking. Results Co-morbid CVD prevalence at 5 months post-diagnosis was 59%, and 16% of participants with no known CVD at the baseline reported de novo CVD by 36 months. Obesity at the baseline predicted de novo hypertension (odds ratio [OR] = 2.20, 95% confidence intervals [CI] = 1.09, 4.45) and de novo diabetes (OR = 6.55, 95% CI = 2.19, 19.53). Participants watching >4 h of TV/d at the baseline (compared with <2 h/d) were more likely to develop ischaemic heart disease by 36 months (OR = 5.51, 95% CI = 1.86, 16.34). Conclusion Overweight colorectal cancer survivors were more likely to suffer from co-morbid CVD. Interventions focusing on weight management and other modifiable lifestyle factors may reduce functional decline and improve survival.

Low frequency of CHEK2 1100delC allele in Australian multiple-case breast cancer families : functional analysis in heterozygous individuals

A protein-truncating variant of CHEK2, 1100delC, is associated with a moderate increase in breast cancer risk. We have determined the prevalence of this allele in index cases from 300 Australian multiple-case breast cancer families, 95% of which had been found to be negative for mutations in BRCA1 and BRCA2. Only two (0.6%) index cases heterozygous for the CHEK2 mutation were identified. All available relatives in these two families were genotyped, but there was no evidence of co-segregation between the CHEK2 variant and breast cancer. Lymphoblastoid cell lines established from a heterozygous carrier contained approximately 20% of the CHEK2 1100delC mRNA relative to wild-type CHEK2 transcript. However, no truncated CHK2 protein was detectable. Analyses of expression and phosphorylation of wild-type CHK2 suggest that the variant is likely to act by haploinsufficiency. Analysis of CDC25A degradation, a downstream target of CHK2, suggests that some compensation occurs to allow normal degradation of CDC25A. Such compensation of the 1100delC defect in CHEK2 might explain the rather low breast cancer risk associated with the CHEK2 variant, compared to that associated with truncating mutations in BRCA1 or BRCA2.

Co-expression of CD147 (EMMPRIN), CD44v3-10, MDR1 and monocarboxylate transporters is associated with prostate cancer drug resistance and progression

Background: The aim of this study is to seek an association between markers of metastatic potential, drug resistance-related protein and monocarboxylate transporters in prostate cancer (CaP). Methods: We evaluated the expression of invasive markers (CD147, CD44v3-10), drug-resistance protein (MDR1) and monocarboxylate transporters (MCT1 and MCT4) in CaP metastatic cell lines and CaP tissue microarrays (n=140) by immunostaining. The co-expression of CD147 and CD44v3-10 with that of MDR1, MCT1 and MCT4 in CaP cell lines was evaluated using confocal microscopy. The relationship between the expression of CD147 and CD44v3-10 and the sensitivity (IC50) to docetaxel in CaP cell lines was assessed using MTT assay. The relationship between expression of CD44v3-10, MDR1 and MCT4 and various clinicopathological CaP progression parameters was examined. Results: CD147 and CD44v3-10 were co-expressed with MDR1, MCT1 and MCT4 in primary and metastatic CaP cells. Both CD147 and CD44v3-10 expression levels were inversely related to docetaxel sensitivity (IC50) in metastatic CaP cell lines. Overexpression of CD44v3-10, MDR1 and MCT4 was found in most primary CaP tissues, and was significantly associated with CaP progression. Conclusions: Our results suggest that the overexpression of CD147, CD44v3-10, MDR1 and MCT4 is associated with CaP progression. Expression of both CD147 and CD44v3-10 is correlated with drug resistance during CaP metastasis and could be a useful potential therapeutic target in advanced disease.

Identification of area-level influences on regions of high cancer incidence in Queensland, Australia : a classification tree approach

Background: Strategies for cancer reduction and management are targeted at both individual and area levels. Area-level strategies require careful understanding of geographic differences in cancer incidence, in particular the association with factors such as socioeconomic status, ethnicity and accessibility. This study aimed to identify the complex interplay of area-level factors associated with high area-specific incidence of Australian priority cancers using a classification and regression tree (CART) approach. Methods: Area-specific smoothed standardised incidence ratios were estimated for priority-area cancers across 478 statistical local areas in Queensland, Australia (1998-2007, n=186,075). For those cancers with significant spatial variation, CART models were used to identify whether area-level accessibility, socioeconomic status and ethnicity were associated with high area-specific incidence. Results: The accessibility of a person’s residence had the most consistent association with the risk of cancer diagnosis across the specific cancers. Many cancers were likely to have high incidence in more urban areas, although male lung cancer and cervical cancer tended to have high incidence in more remote areas. The impact of socioeconomic status and ethnicity on these associations differed by type of cancer. Conclusions: These results highlight the complex interactions between accessibility, socioeconomic status and ethnicity in determining cancer incidence risk.

Randomised controlled trial of a supervised exercise rehabilitation program for colorectal cancer survivors immediately after chemotherapy: study protocol

Background Colorectal cancer (CRC) diagnosis and the ensuing treatments can have a substantial impact on the physical and psychological health of survivors. As the number of CRC survivors increases, so too does the need to develop viable rehabilitation programs to help these survivors return to good health as quickly as possible. Exercise has the potential to address many of the adverse effects of CRC treatment; however, to date, the role of exercise in the rehabilitation of cancer patients immediately after the completion of treatment has received limited research attention. This paper presents the design of a randomised controlled trial which will evaluate the feasibility and efficacy of a 12-week supervised aerobic exercise program (ImPACT Program) on the physiological and psychological markers of rehabilitation, in addition to biomarkers of standard haematological outcomes and the IGF axis. Methods/Design Forty CRC patients will be recruited through oncology clinics and randomised to an exercise group or a usual care control group. Baseline assessment will take place within 4 weeks of the patient completing adjuvant chemotherapy treatment. The exercise program for patients in the intervention group will commence a week after the baseline assessment. The program consists of three supervised moderate-intensity aerobic exercise sessions per week for 12 weeks. All participants will have assessments at baseline (0 wks), mid-intervention (6 wks), post-intervention (12 wks) and at a 6-week follow-up (18 wks). Outcome measures include cardio-respiratory fitness, biomarkers associated with health and survival, and indices of fatigue and quality of life. Process measures are participants' acceptability of, adherence to, and compliance with the exercise program, in addition to the safety of the program. Discussion The results of this study will provide valuable insight into the role of supervised exercise in improving life after CRC. Additionally, process analyses will inform the feasibility of implementing the program in a population of CRC patients immediately after completing chemotherapy.

Risk of second cancer after lymphohematopoietic neoplasm

People living with lymphohematopoietic neoplasms (LHNs) are known to have increased risks of second cancer; however, the incidence of second cancers after LHNs has not been studied extensively in Australia. The Australian Cancer Database was used to analyze site-specific risk of second primary cancer after LHNs in 127,707 patients diagnosed between 1983 and 2005. Standardized incidence ratios (SIRs) were calculated using population rates. Overall, patients with an LHN had nearly twice the risk of developing a second cancer compared to the Australian population. Among 40,321 patients with non-Hodgkin's lymphoma (NHL), there was over a fourfold significant increase in melanoma, Kaposi sarcoma, cancer of the lip, connective tissue and peripheral nerves, eye, thyroid, Hodgkin's disease (HD) and myeloid leukemia. Among 6,396 patients with HD, there was over a fourfold significant increase in melanoma, Kaposi sarcoma, cancer of the lip, oral cavity and pharynx, female breast, uterine cervix, testis, thyroid, NHL and myeloid leukemia. Among the 33,025 patients with lymphoid and myeloid leukemia, significant excess were seen for cancers of the lip, eye, connective tissue and peripheral nerves, NHL and HD. Among the 13,856 patients with plasma cell tumors, there was over fourfold significant increase for melanoma, cancer of the connective tissue and peripheral nerves and myeloid leukemia. Our findings provide evidence of an increased risk of cancer, particularly ultraviolet radiation- and immunosuppression-related cancers, after an LHN in Australia. Copyright © 2010 UICC.