Incidence, risk factors and estimates of a woman's risk of developing secondary lower limb lymphedema and lymphedema-specific supportive care needs in women treated for endometrial cancer

Objectives: Few studies have assessed the risk and impact of lymphedema among women treated for endometrial cancer. We aimed to quantify cumulative incidence of, and risk factors for developing lymphedema following treatment for endometrial cancer and estimate absolute risk for individuals. Further, we report unmet needs for help with lymphedema-specific issues. Methods: Women treated for endometrial cancer (n = 1243) were followed-up 3–5 years after diagnosis; a subset of 643 completed a follow-up survey that asked about lymphedema and lymphedema-related support needs. We identified a diagnosis of secondary lymphedema from medical records or self-report. Multivariable logistic regression was used to evaluate risk factors and estimates. Results: Overall, 13% of women developed lymphedema. Risk varied markedly with the number of lymph nodes removed and, to a lesser extent, receipt of adjuvant radiation or chemotherapy treatment, and use of nonsteroidal anti-inflammatory drugs (pre-diagnosis). The absolute risk of developing lymphedema was > 50% for women with 15 + nodes removed and 2–3 additional risk factors, 30–41% for those with 15 + nodes removed plus 0–1 risk factors or 6–14 nodes removed plus 3 risk factors, but ≤ 8% for women with no nodes removed or 1–5 nodes but no additional risk factors. Over half (55%) of those who developed lymphedema reported unmet need(s), particularly with lymphedema-related costs and pain. Conclusion: Lymphedema is common; experienced by one in eight women following endometrial cancer. Women who have undergone lymphadenectomy have very high risks of lymphedema and should be informed how to self-monitor for symptoms. Affected women need greater levels of support.

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.

Can skin cancer prevention and early detection be improved via mobile phone text messaging? a randomised, attention-control trial.

Objective. To test the impact of a theory-based, SMS (text message)-delivered behavioural intervention (Healthy Text) targeting sun protection or skin self-examination behaviours compared to attention-control. Method. Overall, 546 participants aged 18–42 years were randomised using a computer-generated number list to the skin self-examination (N = 176), sun protection (N = 187), or attention-control (N = 183) text messages group. Each group received 21 text messages about their assigned topic over 12 months (12 weekly messages for three months, then monthly messages for the next nine months). Data was collected via telephone survey at baseline, three-, and 12-months across Queensland from January 2012 to August 2013. Results. One year after baseline, the sun protection (mean change 0.12; P = 0.030) and skin self-examination groups (mean change 0.12; P = 0.035) had significantly greater improvement in their sun protection habits (SPH) index compared to the attention-control group (reference mean change 0.02). The increase in the proportion of participants who reported any skin self-examination from baseline to 12 months was significantly greater in the skin self-examination intervention group (103/163; 63%; P < 0.001) than the sun protection (83/173; 48%), or attention-control (65/165; 36%) groups. There was no significant effect of the intervention for participants who self-reported whole-body skin self-examination, sun tanning behaviour, or sunburn behaviours. Conclusion. The Healthy Text intervention was effective in inducing significant improvements in sun protection and any type of skin self-examination behaviours.

Systematic review of pharmacologic and non-pharmacologic interventions to manage cognitive alterations after chemotherapy for breast cancer

Purpose Cognitive alterations are reported in breast cancer patients receiving chemotherapy. This has adverse effects on patients’ quality of life and function. This systematic review investigates the effectiveness of pharmacologic and non-pharmacologic interventions to manage cognitive alterations associated with breast cancer treatment. Methods Medline via EBSCOhost, CINAHL and Cochrane CENTRAL were searched for the period January 1999 to May 2014 for prospective randomized controlled trials related to the management of chemotherapy-associated cognitive alterations. Included studies investigated the management of chemotherapy-associated cognitive alterations and used subjective or objective measures in patients with breast cancer during or after chemotherapy. Two authors independently extracted data and assessed the risk of bias. Results Thirteen studies involving 1138 participants were included. Overall, the risk of bias for the 13 studies were either high (n=11) or unclear (n=2). Pharmacologic interventions included psychostimulants (n=4), epoetin alfa (n=1), and Ginkgo biloba (n=1). Non-pharmacologic interventions were cognitive training (n=5) and physical activity (n=2). Pharmacologic agents were ineffective except for self-reported cognitive function in an epoetin alfa study. Cognitive training interventions demonstrated benefits in self-reported cognitive function, memory, verbal function and language and orientation/attention. Physical activity interventions were effective in improving executive function and self-reported concentration. Conclusion Current evidence does not favor the pharmacologic management of cognitive alterations associated with breast cancer treatment. Cognitive training and physical activity interventions appear promising, but additional studies are required to establish their efficacy. Further research is needed to overcome methodological shortfalls such as heterogeneity in participant characteristics and non-standardized neuropsychological outcome measures.

Epidemiology and risk factors of oral cancer in South Africa

Head and neck cancers are some of the leading cancers in the coloured and black South African male population and the perception exists that the incidence rates are rising. Aims: To determine the standardised morbidity rates and some of the risk factors for oral cancer in South Africa. Methods: Using histologically verified data from the National Cancer Registry, the age standardised incidence rates (ASIR) and life-time risks (LR) of oral cancer in South Africa were calculated for 1988-1991.2. In an ongoing case control study (1995 +) among black patients in Johannesburg/Soweto, adjusted odds ratios for developing oral cancers in relation to tobacco and alcohol consumption were calculated. Results: Coloured males vs. females: ASIR 13.13 vs. 3.5 (/100,000/year), LR 1:65 vs. 1:244. Black males vs. females: ASIR 9.06 vs. 1.75, LR 1:86 and 1:455. White males vs. females: ASIR 8.06 vs. 3.18, LR 1:104 vs. 1:278. Asian males vs. females: ASIR 5.24 vs. 6.66, LR 1:161 vs. 1:125. The odds ratio for oral cancer in black males in relation to smoking was 7.0 (95% CI 3.0-14.6) and daily alcohol consumption 1.3 (95% CI 0.6-2.8). In black females the odds ratios in relation to smoking were 3.9 (95% CI 1.7 8.9) and daily alcohol consumption 1.7(95% CI 0.7-4.1). Conclusions: The risk factors for oral cancer in South Africa are multiple and gender discrepancies in ASIR and LR signal differences in exposure to carcinogens. It is unclear whether the incidence of oral cancers will rise in the future.

Androgen-targeted therapy-induced epithelial mesenchymal plasticity and neuroendocrine transdifferentiation in prostate cancer : an opportunity for intervention

Androgens regulate biological pathways to promote proliferation, differentiation, and survival of benign and malignant prostate tissue. Androgen receptor (AR) targeted therapies exploit this dependence and are used in advanced prostate cancer to control disease progression. Contemporary treatment regimens involve sequential use of inhibitors of androgen synthesis or AR function. Although targeting the androgen axis has clear therapeutic benefit, its effectiveness is temporary, as prostate tumor cells adapt to survive and grow. The removal of androgens (androgen deprivation) has been shown to activate both epithelial-to-mesenchymal transition (EMT) and neuroendocrine transdifferentiation (NEtD) programs. EMT has established roles in promoting biological phenotypes associated with tumor progression (migration/invasion, tumor cell survival, cancer stem cell-like properties, resistance to radiation and chemotherapy) in multiple human cancer types. NEtD in prostate cancer is associated with resistance to therapy, visceral metastasis, and aggressive disease. Thus, activation of these programs via inhibition of the androgen axis provides a mechanism by which tumor cells can adapt to promote disease recurrence and progression. Brachyury, Axl, MEK, and Aurora kinase A are molecular drivers of these programs, and inhibitors are currently in clinical trials to determine therapeutic applications. Understanding tumor cell plasticity will be important in further defining the rational use of androgen-targeted therapies clinically and provides an opportunity for intervention to prolong survival of men with metastatic prostate cancer.

User preferences for text message-delivered skin cancer prevention and early detection

Evidence is needed for the acceptability and user preferences of receiving skin cancer-related text messages. We prepared 27 questions to evaluate attitudes, satisfaction with program characteristics such as timing and spacing, and overall satisfaction with the Healthy Text program in young adults. Within this randomised controlled trial (age 18-42 years), 546 participants were assigned to one of three Healthy Text message groups; sun protection, skin self-examination, or attention-control. Over a 12-month period, 21 behaviour-specific text messages were sent to each group. Participants’ preferences were compared between the two interventions and control group at the 12-month follow-up telephone interview. In all three groups, participants reported the messages were easy to understand (98%), provided good suggestions or ideas (88%), and were encouraging (86%) and informative (85%) with little difference between the groups. The timing of the texts was received positively (92%); however, some suggestions for frequency or time of day the messages were received from 8% of participants. Participants in the two intervention groups found their messages more informative, and triggering behaviour change compared to control. Text messages about skin cancer prevention and early detection are novel and acceptable to induce behaviour change in young adults.

A systematic review of patient-reported outcome instruments of dermatologic adverse events associated with targeted cancer therapies

Purpose Dermatologic adverse events (dAEs) in cancer treatment are frequent with the use of targeted therapies. These dAEs have been shown to have significant impact on health-related quality of life (HRQoL). While standardized assessment tools have been developed for physicians to assess severity of dAEs, there is a discord between objective and subjective measures. The identification of patient-reported outcome (PRO) instruments useful in the context of targeted cancer therapies is therefore important in both the clinical and research settings for the overall evaluation of dAEs and their impact on HRQoL. Methods A comprehensive, systematic literature search of published articles was conducted by two independent reviewers in order to identify PRO instruments previously utilized in patient populations with dAEs from targeted cancer therapies. The identified PRO instruments were studied to determine which HRQoL issues relevant to dAEs were addressed, as well as the process of development and validation of these instruments. Results Thirteen articles identifying six PRO instruments met the inclusion criteria. Four instruments were general dermatology (Skindex-16©, Skindex-29©, Dermatology Life Quality Index (DLQI), and DIELH-24) and two were symptom-specific (functional assessment of cancer therapy-epidermal growth factor receptor inhibitor-18 (FACT-EGFRI-18) and hand-foot syndrome-14 (HFS-14)). Conclusions While there are several PRO instruments that have been tested in the context of targeted cancer therapy, additional work is needed to develop new instruments and to further validate the instruments identified in this study in patients receiving targeted therapies.

Repositioning "old" drugs for new causes : identifying new treatments for prostate cancer

The majority of prostate cancer related deaths are due to the spread of the disease. This project developed a screening protocol to identify existing drugs that could be used to prevent the spread of prostate cancer and thereby improve the survival of the patients.

Parent feeding interactions and practices during childhood cancer treatment: A qualitative investigation

In the general population it is evident that parent feeding practices can directly shape a child’s life long dietary intake. Young children undergoing childhood cancer treatment may experience feeding difficulties and limited food intake, due to the inherent side effects of their anti-cancer treatment. What is not clear is how these treatment side effects are influencing the parent–child feeding relationship during anti-cancer treatment. This retrospective qualitative study collected telephone based interview data from 38 parents of childhood cancer patients who had recently completed cancer treatment (child’s mean age: 6.98 years). Parents described a range of treatment side effects that impacted on their child’s ability to eat, often resulting in weight loss. Sixty-one percent of parents (n = 23) reported high levels of stress in regard to their child’s eating and weight loss during treatment. Parents reported stress, feelings of helplessness, and conflict and/or tension between parent and the child during feeding/eating interactions. Parents described using both positive and negative feeding practices, such as: pressuring their child to eat, threatening the insertion of a nasogastric feeding tube, encouraging the child to eat and providing home cooked meals in hospital. Results indicated that parent stress may lead to the use of coping strategies such as positive or negative feeding practices to entice their child to eat during cancer treatment. Future research is recommended to determine the implication of parent feeding practice on the long term diet quality and food preferences of childhood cancer survivors.

Establishing prostate cancer patient derived xenografts: Lessons learned from older studies

Background Understanding the progression of prostate cancer to androgen-independence/castrate resistance and development of preclinical testing models are important for developing new prostate cancer therapies. This report describes studies performed 30 years ago, which demonstrate utility and shortfalls of xenografting to preclinical modeling. Methods We subcutaneously implanted male nude mice with small prostate cancer fragments from transurethral resection of the prostate (TURP) from 29 patients. Successful xenografts were passaged into new host mice. They were characterized using histology, immunohistochemistry for marker expression, flow cytometry for ploidy status, and in some cases by electron microscopy and response to testosterone. Two xenografts were karyotyped by G-banding. Results Tissues from 3/29 donors (10%) gave rise to xenografts that were successfully serially passaged in vivo. Two, (UCRU-PR-1, which subsequently was replaced by a mouse fibrosarcoma, and UCRU-PR-2, which combined epithelial and neuroendocrine features) have been described. UCRU-PR-4 line was a poorly differentiated prostatic adenocarcinoma derived from a patient who had undergone estrogen therapy and bilateral castration after his cancer relapsed. Histologically, this comprised diffusely infiltrating small acinar cell carcinoma with more solid aggregates of poorly differentiated adenocarcinoma. The xenografted line showed histology consistent with a poorly differentiated adenocarcinoma and stained positively for prostatic acid phosphatase (PAcP), epithelial membrane antigen (EMA) and the cytokeratin cocktail, CAM5.2, with weak staining for prostate specific antigen (PSA). The line failed to grow in female nude mice. Castration of three male nude mice after xenograft establishment resulted in cessation of growth in one, growth regression in another and transient growth in another, suggesting that some cells had retained androgen sensitivity. The karyotype (from passage 1) was 43–46, XY, dic(1;12)(p11;p11), der(3)t(3:?5)(q13;q13), -5, inv(7)(p15q35) x2, +add(7)(p13), add(8)(p22), add(11)(p14), add(13)(p11), add(20)(p12), -22, +r4[cp8]. Conclusions Xenografts provide a clinically relevant model of prostate cancer, although establishing serially transplantable prostate cancer patient derived xenografts is challenging and requires rigorous characterization and high quality starting material. Xenografting from advanced prostate cancer is more likely to succeed, as xenografting from well differentiated, localized disease has not been achieved in our experience. Strong translational correlations can be demonstrated between the clinical disease state and the xenograft model

The burden of cancer in member countries of the association of southeast asian nations (ASEAN)

This paper presents the most recent data on cancer rates and the burden of cancer in the ASEAN region. Epidemiological data were sourced from GLOBOCAN 2008 and disability adjusted life years (DALYs) lost were estimated using the standard methodology developed within the World Health Organization's Global Burden of Disease study. Overall, it was estimated there were over 700,000 new cases of cancer and 500,000 cancer deaths in ASEAN in the year 2008, leading to approximately 7.5 million DALYs lost in one year. The most commonly diagnosed cancers were lung (98,143), breast (86,842) and liver cancers (74,777). The most common causes of cancer death were lung cancer (85,772), liver cancer (69,115) and colorectal cancer (44,280). The burden of cancer in terms of DALYs lost was highest in Laos, Viet Nam and Myanmar and lowest in Brunei, Singapore and the Philippines. Significant differences in the patterns of cancer from country to country were observed. Another key finding was the major impact played by population age distribution on cancer incidence and mortality. Cancer rates in ASEAN are expected to increase with ageing of populations and changes in lifestyles associated with economic development. Therefore, ASEAN member countries are strongly encouraged to put in place cancer-control health carepolicies, focussed on strengthening the health systems to cope with projected increases in cancer prevention, treatment and management needs.

Antibodies against human herpesvirus 8 in black South African patients with cancer

Background Infection with human herpesvirus 8 (HHV-8) has been consistently linked to Kaposi's sarcoma, but its mode of transmission, association with other cancers, and interaction with the human immunodeficiency virus type 1 (HIV-1) are largely unknown. Methods Between January 1992 and December 1997, we interviewed 3591 black patients with cancer in Johannesburg and Soweto, South Africa. Blood was tested for antibodies against HIV-1 and HHV-8 in 3344 of the patients. Antibodies against HHV-8 were detected with an indirect immunofluorescence assay. The intensity of the fluorescent signal correlated well with the titers of antibodies (P<0.001). The relations among the presence of anti–HHV-8 antibodies, sociodemographic and behavioral factors, type of cancer, and the presence or absence of coexistent HIV-1 infection were examined with the use of unconditional logistic-regression models. Results Among the 3293 subjects with cancers other than Kaposi's sarcoma, the standardized seroprevalence of antibodies against HHV-8 was 32 percent, which did not differ significantly from the standardized seroprevalence among black blood donors. Among these 3293 patients, the prevalence of antibodies against HHV-8 increased with increasing age (P<0.001) and an increasing number of sexual partners (P=0.05) and decreased with increasing years of education (P=0.007); it was not strongly associated with HIV-1 infection. Anti–HHV-8 antibodies were more frequent among black than white blood donors (P<0.001). Among the 51 patients with Kaposi's sarcoma, the standardized seroprevalence of antibodies against HHV-8 was 83 percent, significantly higher than the prevalence among those without Kaposi's sarcoma (P<0.001). For 16 other specific types of cancer, including multiple myeloma (108 cases) and prostate cancer (202 cases), the variation in the standardized seroprevalence of antibodies against HHV-8 was not remarkable. At a given intensity of fluorescence of anti–HHV-8 antibodies, Kaposi's sarcoma was more frequent among HIV-1–positive patients than among those who were HIV-1–negative (P<0.001). Conclusions Among black patients with cancer in South Africa, the seroprevalence of anti–HHV-8 antibodies is high and is specifically associated with Kaposi's sarcoma, particularly at high titers.

A multimodal physiotherapy programme plus deep water running for improving cancer-related fatigue and quality of life in breast cancer survivors

The aim of the study was to assess the feasibility and effectiveness of aquatic‐based exercise in the form of deep water running ( DWR ) as part of a multimodal physiotherapy programme ( MMPP ) for breast cancer survivors. A controlled clinical trial was conducted in 42 primary breast cancer survivors recruited from community‐based P rimary C are C entres. Patients in the experimental group received a MMPP incorporating DWR , 3 times a week, for an 8‐week period. The control group received a leaflet containing instructions to continue with normal activities. Statistically significant improvements and intergroup effect size were found for the experimental group for P iper F atigue S cale‐ R evised total score ( d = 0.7, P = 0.001), as well as behavioural/severity ( d = 0.6, P = 0.05), affective/meaning ( d = 1.0, P = 0.001) and sensory ( d = 0.3, P = 0.03) domains. Statistically significant differences between the experimental and control groups were also found for general health ( d = 0.5, P < 0.05) and quality of life ( d = 1.3, P < 0.05). All participants attended over 80% of sessions, with no major adverse events reported. The results of this study suggest MMPP incorporating DWR decreases cancer‐related fatigue and improves general health and quality of life in breast cancer survivors. Further, the high level of adherence and lack of adverse events indicate such a programme is safe and feasible.