Radiobiological model comparison of 3D conformal radiotherapy and IMRT plans for the treatment of prostate cancer

The main aim of radiotherapy is to deliver a dose of radiation that is high enough to destroy the tumour cells while at the same time minimising the damage to normal healthy tissues. Clinically, this has been achieved by assigning a prescription dose to the tumour volume and a set of dose constraints on critical structures. Once an optimal treatment plan has been achieved the dosimetry is assessed using the physical parameters of dose and volume. There has been an interest in using radiobiological parameters to evaluate and predict the outcome of a treatment plan in terms of both a tumour control probability (TCP) and a normal tissue complication probability (NTCP). In this study, simple radiobiological models that are available in a commercial treatment planning system were used to compare three dimensional conformal radiotherapy treatments (3D-CRT) and intensity modulated radiotherapy (IMRT) treatments of the prostate. Initially both 3D-CRT and IMRT were planned for 2 Gy/fraction to a total dose of 60 Gy to the prostate. The sensitivity of the TCP and the NTCP to both conventional dose escalation and hypo-fractionation was investigated. The biological responses were calculated using the Källman S-model. The complication free tumour control probability (P+) is generated from the combined NTCP and TCP response values. It has been suggested that the alpha/beta ratio for prostate carcinoma cells may be lower than for most other tumour cell types. The effect of this on the modelled biological response for the different fractionation schedules was also investigated.

Exploring non-cancer pain conditions in a community sample : critiquing a current conceptual model of the acute to chronic pain transition and examining predictors of chronicity

This program of research examines the experience of chronic pain in a community sample. While, it is clear that like patient samples, chronic pain in non-patient samples is also associated with psychological distress and physical disability, the experience of pain across the total spectrum of pain conditions (including acute and episodic pain conditions) and during the early course of chronic pain is less clear. Information about these aspects of the pain experience is important because effective early intervention for chronic pain relies on identification of people who are likely to progress to chronicity post-injury. A conceptual model of the transition from acute to chronic pain was proposed by Gatchel (1991a). In brief, Gatchel’s model describes three stages that individuals who have a serious pain experience move through, each with worsening psychological dysfunction and physical disability. The aims of this program of research were to describe the experience of pain in a community sample in order to obtain pain-specific data on the problem of pain in Queensland, and to explore the usefulness of Gatchel’s Model in a non-clinical sample. Additionally, five risk factors and six protective factors were proposed as possible extensions to Gatchel’s Model. To address these aims, a prospective longitudinal mixed-method research design was used. Quantitative data was collected in Phase 1 via a comprehensive postal questionnaire. Phase 2 consisted of a follow-up questionnaire 3 months post-baseline. Phase 3 consisted of semi-structured interviews with a subset of the original sample 12 months post follow-up, which used qualitative data to provide a further in-depth examination of the experience and process of chronic pain from respondents’ point of view. The results indicate chronic pain is associated with high levels of anxiety and depressive symptoms. However, the levels of disability reported by this Queensland sample were generally lower than those reported by clinical samples and consistent with disability data reported in a New South Wales population-based study. With regard to the second aim of this program of research, while some elements of the pain experience of this sample were consistent with that described by Gatchel’s Model, overall the model was not a good fit with the experience of this non-clinical sample. The findings indicate that passive coping strategies (minimising activity), catastrophising, self efficacy, optimism, social support, active strategies (use of distraction) and the belief that emotions affect pain may be important to consider in understanding the processes that underlie the transition to and continuation of chronic pain.

Implication of 3D culture system for study of prostate cancer (CaP) mediated bone metastasis

Introduction : For the past decade, three dimensional (3D) culture has served as a foundation for regenerative medicine study. With an increasing awareness of the importance of cell-cell and cell-extracellular matrix interactions which are lacking in 2D culture system, 3D culture system has been employed for many other applications namely cancer research. Through development of various biomaterials and utilization of tissue engineering technology, many in vivo physiological responses are now better understood. The cellular and molecular communication of cancer cells and their microenvironment, for instance can be studied in vitro in 3D culture system without relying on animal models alone. Predilection of prostate cancer (CaP) to bone remains obscure due to the complexity of the mechanisms and lack of proper model for the studies. In this study, we aim to investigate the interaction between CaP cells and osteoblasts simulating the natural bone metastasis. We also further investigate the invasiveness of CaP cells and response of androgen sensitve CaP cells, LNCaP to synthetic androgen.----- Method : Human osteoblast (hOB) scaffolds were prepared by seeding hOB on medical grade polycaprolactone-tricalcium phosphate (mPLC-TCP) scaffolds and induced to produce bone matrix. CaP cell lines namely wild type PC3 (PC3-N), overexpressed prostate specific antigen PC3 (PC3k3s5) and LNCaP were seeded on hOB scaffolds as co-cultures. Morphology of cells was examined by Phalloidin-DAPI and SEM imaging. Gelatin zymography was performed on the 48 hours conditioned media (CM) from co-cultures to determine matrix metalloproteinase (MMP) activity. Gene expression of hOB/LNCaP co-cultures which were treated for 48 hours with 1nM synthetic androgen R1881 were analysed by quantitative real time PCR (qRT-PCR).----- Results : Co-culture of PCC/hOB revealed that the morphology of PCCs on the tissue engineered bone matrix varied from homogenous to heterogenous clusters. Enzymatically inactive pro-MMP2 was detected in CM from hOBs and PCCs cultured on scaffolds. Elevation in MMP9 activity was found only in hOB/PC3N co-culture. hOB/LNCaP co-culture showed increase in expression of key enzymes associated with steroid production which also corresponded to an increase in prostate specific antigen (PSA) and MMP9.----- Conclusions : Upregulation of MMP9 indicates involvement of ECM degradation during cancer invasion and bone metastases. Expression of enzymes involved in CaP progression, PSA, which is not expressed in osteoblasts, demonstrates that crosstalk between PCCs and osteoblasts may play a part in the aggressiveness of CaP. The presence of steroidogenic enzymes, particularly, RDH5, in osteoblasts and stimulated expression in co-culture, may indicate osteoblast production of potent androgens, fuelling cancer cell proliferation. Based on these results, this practical 3D culture system may provide greater understanding into CaP mediated bone metastasis. This allows the role of the CaP/hOB interaction with regards to invasive property and steroidogenesis to be further explored.

International epidemiology of prostate cancer : geographical distribution and secular trends

This review outlines current international patterns in prostate cancer incidence and mortality rates and survival, including recent trends and a discussion of the possible impact of prostate-specific antigen (PSA) testing on the observed data. Internationally, prostate cancer is the second most common cancer diagnosed among men (behind lung cancer), and is the sixth most common cause of cancer death among men. Prostate cancer is particularly prevalent in developed countries such as the United States and the Scandinavian countries, with about a six-fold difference between high-incidence and low-incidence countries. Interpretation of trends in incidence and survival are complicated by the increasing impact of PSA testing, particularly in more developed countries. As Western influences become more pronounced in less developed countries, prostate cancer incidence rates in those countries are tending to increase, even though the prevalence of PSA testing is relatively low. Larger proportions of younger men are being diagnosed with prostate cancer and living longer following diagnosis of prostate cancer, which has many implications for health systems. Decreasing mortality rates are becoming widespread among more developed countries, although it is not clear whether this is due to earlier diagnosis (PSA testing), improved treatment, or some combination of these or other factors.

The impact of perceived stage of cancer on carers’ anxiety and depression during the patients’ final year of life

Objective: This paper explores the effects of perceived stage of cancer (PSOC) on carers' anxiety and depression during the patients' final year. Methods: A consecutive sample of patients and carers (N=98) were surveyed at regular intervals regarding PSOC, and anxiety and depression using the Hospital Anxiety and Depression Scale. Means were compared by gender using the Mann-Whitney U-test. The chi-square was used to analyse categorical data. Agreement between carers' and patients' PSOC was estimated using kappa statistics. Correlations between carers' PSOC and their anxiety and depression were calculated using the Spearman's rank correlation. Results: Over time, an increasing proportion of carers reported that the cancer was advanced, culminating at 43% near death. Agreement regarding PSOC was fair (kappa=0.29-0.34) until near death (kappa=0.21). Carers' anxiety increased over the year; depression increased in the final 6 months. Females were more anxious (p=0.049, 6 months; p=0.009, 3 months) than males, and more depressed until 1 month to death. The proportion of carers reporting moderate-severe anxiety almost doubled over the year to 27%, with more females in this category at 6 months (p=0.05). Carers with moderate-severe depression increased from 6 to 15% over the year. Increased PSOC was weakly correlated with increased anxiety and depression. Conclusions: Carers' anxiety exceeded depression in severity during advanced cancer. Females generally experienced greater anxiety and depression. Carers were more realistic than patients regarding the ultimate outcome, which was reflected in their declining mental health, particularly near the end.

A qualitative study of the experience of oral cancer among Taiwanese men

The incidence and mortality of oral cancer in Taiwanese men have increased over the past decade, primarily associated with a surge in the popularity of betel quid chewing. The aim of this study was to examine the experience of six Taiwanese men with oral cancer, who were aged between 40 and 60 years, using a qualitative approach. The three major themes emerging from the data include: (i) understanding the cancer diagnosis; (ii) the challenges of cancer treatment; and (iii) adapting to difference. Increasing nurses' understanding of the experiential aspects of oral cancer in this population is required if nurses are to develop successful health promotion programmes and nursing interventions to meet these patients' needs.

Incomplete pregnancy and risk of ovarian cancer : results from two Australian case-control studies and systematic review

Although full-term pregnancies reduce the risk of ovarian cancer, it has not been conclusively established whether incomplete pregnancies also influence risk. We investigated the relationship between a history of incomplete pregnancy and incident epithelial ovarian cancer among over 4,500 women who participated in two large Australian population-based case-control studies in 1990-1993 and 2002-2005. They provided responses to detailed questions about their reproductive histories and other personal factors. Summary odds ratios (OR) and confidence intervals (CI) derived from each study using the same covariates were aggregated. We found no significant associations between the number of incomplete pregnancies and ovarian cancer, for parous (OR = 0.98, 95% CI: 0.89, 1.08) or nulliparous (OR = 1.06, 95% CI: 0.75, 1.48) women, nor for the number of spontaneous or induced abortions and ovarian cancer for parous women (OR = 0.95, 95% CI 0.82, 1.09; OR = 1.08, 95% CI: 0.86, 1.36) or nulliparous women (OR = 1.2, 95% CI: 0.6, 2.4; OR = 0.8, 95% CI: 0.47, 1.38), respectively. A systematic review of 37 previous studies of the topic confirmed our findings that a history of incomplete pregnancy does not influence a woman’s risk of epithelial ovarian cancer.

Effects and feasibility of a multi-disciplinary orientation program for newly registered cancer patients : design of a randomised controlled trial

Background Diagnosis and treatment of cancer can contribute to psychological distress and anxiety amongst patients. Evidence indicates that information giving can be beneficial in reducing patient anxiety, so oncology specific information may have a major impact on this patient group. This study investigates the effects of an orientation program on levels of anxiety and self-efficacy amongst newly registered cancer patients who are about to undergo chemotherapy and/or radiation therapy in the cancer care centre of a large tertiary Australian hospital. Methods The concept of interventions for orienting new cancer patients needs revisiting due to the dynamic health care system. Historically, most orientation programs at this cancer centre were conducted by one nurse. A randomised controlled trial has been designed to test the effectiveness of an orientation program with bundled interventions; a face-to-face program which includes introduction to the hospital facilities, introduction to the multi-disciplinary team and an overview of treatment side effects and self care strategies. The aim is to orientate patients to the cancer centre and to meet the health care team. We hypothesize that patients who receive this orientation will experience lower levels of anxiety and distress, and a higher level of self-efficacy. Discussion An orientation program is a common health care service provided by cancer care centres for new cancer patients. Such programs aim to give information to patients at the beginning of their encounter at a cancer care centre. It is clear in the literature that interventions that aim to improve self-efficacy in patients may demonstrate potential improvement in health outcomes. Yet, evidence on the effects of orientation programs for cancer patients on self-efficacy remains scarce, particularly with respect to the use of multidisciplinary team members. This paper presents the design of a randomised controlled trial that will evaluate the effects and feasibility of a multidisciplinary orientation program for new cancer patients.

Exercise for health : a breast cancer recovery program - quality of life benefits [Conference Abstract]

Introduction: Five-year survival from breast cancer in Australia is 87%. Hence, ensuring a good quality of life (QOL) has become a focal point of cancer research and clinical interest. Exercise during and after treatment has been identified as a potential strategy to optimise QOL of women diagnosed with breast cancer.----- Methods: Exercise for Health is a randomised controlled trial of an eight-month, exercise intervention delivered by Exercise Physiologists. An objective of this study was to assess the impact of the exercise program during and following treatment on QOL. Queensland women diagnosed with unilateral breast cancer in 2006/07 were eligible to participate. Those living in urban-Brisbane (n=194) were allocated to either the face-to-face exercise group, the telephone exercise group, or the usual-care group, and those living in rural Queensland (n=143) were allocated to the telephone exercise group or the usual-care group. QOL, as assessed by the Functional Assessment of Cancer Therapy-Breast (FACT-B+4) questionnaire, was measured at 4-6 weeks (pre-intervention), 6 months (mid-intervention) and 12 months (three months post-intervention) post-surgery.----- Results: Significant (P<0.01) increases in QOL were observed between pre-intervention and three months post-intervention 12 months post-surgery for all women. Women in the exercise groups experienced greater mean positive changes in QOL during this time (+10 points) compared with the usual-care groups (+5 to +7 points) after adjusting for baseline QOL. Although all groups experienced an overall increase in QOL, approximately 20% of urban and rural women in the usual-care groups reported a decline in QOL, compared with 10% of women in the exercise groups.----- Conclusions: This work highlights the potential importance of participating in physical activity to optimise QOL following a diagnosis of breast cancer. Results suggest that the telephone may be an effective medium for delivering exercise counselling to newly diagnosed breast cancer patients.

The prognostic significance of quality of life following breast cancer [Conference Abstract]

Introduction: Evidence suggests a positive association between quality of life (QOL). and overall survival(OS). among metastatic breast cancer (BC). patients, although the relationship in early-stage BC is unclear. This work examines the association between QOL and OS following a diagnosis of early-stage BC. ----- Methods: A population-based sample of Queensland women (n=287). with early-stage, invasive, unilateral BC, were prospectively observed for a median of 6.6 years. QOL was assessed at six and 18 months post-diagnosis using the Functional Assessment of Cancer Therapy, Breast FACT-B+4. questionnaire. Raw scores for the FACT-B+4 scales were computed and individuals were categorised according to whether QOL declined, remained stable or improved over time. OS was measured from the date of diagnosis to the date of death or was censored at the date of last follow-up. Risk ratios (RR) and 95% confidence intervals (CI). for the association between QOL and OS were obtained using Cox proportional hazards survival models adjusted for confounding characteristics. ----- Results: A total of 27 (9.4%). women died during the follow-up period. Three baseline QOL scales (emotional, general and overall QOL) were significantly associated with OS, with RRs ranging between 0.89 95% CI: 0.81, 0.98; P=0.01. and 0.98 (95% CI: 0.96, 0.99; P=0.03),indicating a 2%-11% reduced risk of death for every one unit increase in QOL. When QOL was categorised according to changes between six and 18 months post-diagnosis, analyses showed that for those who experienced declines in functional and physical QOL, risk of death increased by two- (95% CI: 1.43, 12.52; P<0.01) and four-fold (95% CI: 1.15, 7.19; P=0.02), respectively. Conclusions: This work indicates that specific QOL scales at six months post-diagnosis, and changes in certain QOL scales over the subsequent 12-month period (as measured by the FACT-B+4), are associated with overall survival in women with early-stage breast cancer.

Longitudinal patterns of weight in women diagnosed with breast cancer [Conference Abstract]

Introduction: Weight gain is a common concern following breast cancer and has been associated with negative health outcomes. As such, prevention of weight gain is of clinical interest. This work describes weight change between 6- and 18-months following a breast cancer diagnosis and explores the personal, treatment and behavioural characteristics associated with gains in weight. Methods: Body mass index was objectively assessed, at three-monthly intervals, on a population-based sample of women newly diagnosed with unilateral breast cancer (n=185). Changes in BMI between 6- and 18-months post-diagnosis were calculated, with gains of one or more being considered clinically detrimental to future health. Results: Approximately 60% of participants were overweight or obese at 6-months post-diagnosis. While BMI remained relatively stable across the testing period (range=27.3-27.8), 24% of participants experienced clinically relevant gains in BMI (median gains=1.9). Following adjustment for potential confounders, younger age (<45 years; Odds ratio, OR=9.8), being morbidly obese at baseline (OR=4.6) and receiving hormone therapy (OR=4.8) were characteristics associated with an increased odds (p<0.05) of gaining BMI. Other characteristics associated with gains in BMI were more extensive surgery and having a history of smoking, although these relationships were not supported statistically. In contrast, caring for younger children was associated with reduced risk of gaining BMI (OR=0.3, p=0.20). Conclusions: Clinically relevant weight gain between 6- and 18-months post-breast cancer diagnosis is an issue for one in four women, with certain subgroups being particularly susceptible. However, the majority of women diagnosed with breast cancer are overweight or obese and gains in body weight are common. Thus, interventions that address the importance of achieving and sustaining a healthy body weight, delivered to all women with breast cancer, may have greater public health impact than interventions targeting any specific breast cancer subgroup.

Parent and child experiences of childhood cancer : an interpretative phenomenological analysis approach

A diagnosis of cancer represents a significant crisis for the child and their family. As the treatment for childhood cancer has improved dramatically over the past three decades, most children diagnosed with cancer today survive this illness. However, it is still an illness which severely disrupts the lifestyle and typical functioning of the family unit. Most treatments for cancer involve lengthy hospital stays, the endurance of painful procedures and harsh side effects. Research has confirmed that to manage and adapt to such a crisis, families must undertake measures which assist their adjustment. Variables such as level of family support, quality of parents’ marital relationship, coping of other family members, lack of other concurrent stresses and open communication within the family have been identified as influences on how well families adjust to a diagnosis of childhood cancer. Theoretical frameworks such as the Resiliency Model of Family Adjustment and Adaptation (McCubbin and McCubbin, 1993, 1996) and the Stress and Coping Model by Lazarus and Folkman (1984) have been used to explain how families and individuals adapt to crises or adverse circumstances. Developmental theories have also been posed to account for how children come to understand and learn about the concept of illness. However more descriptive information about how families and children in particular, experience and manage a diagnosis of cancer is still needed. There are still many unanswered questions surrounding how a child adapts to, understands and makes meaning from having a life-threatening illness. As a result, developing an understanding of the impact that such a serious illness has on the child and their family is crucial. A new approach to examining childhood illness such as cancer is currently underway which allows for a greater understanding of the experience of childhood cancer to be achieved. This new approach invites a phenomenological method to investigate the perspectives of those affected by childhood cancer. In the current study 9 families in which there was a diagnosis of childhood cancer were interviewed twice over a 12 month period. Using the qualitative methodology of Interpretative Phenomenological Analysis (IPA) a semi-structured interview was used to explicate the experience of childhood cancer from both the parent and child’s perspectives. A number of quantitative measures were also administered to gather specific information on the demographics of the sample population. The results of this study revealed a number of pertinent areas which need to be considered when treating such families. More importantly experiences were explicated which revealed vital phenomena that needs to be added to extend current theoretical frameworks. Parents identified the time of the diagnosis as the hardest part of their entire experience. Parents experienced an internal struggle when they were forced to come to the realization that they were not able to help their child get well. Families demonstrated an enormous ability to develop a new lifestyle which accommodated the needs of the sick child, as the sick child became the focus of their lives. Regarding the children, many of them accepted their diagnosis without complaint or question, and they were able to recognise and appreciate the support they received. Physical pain was definitely a component of the children’s experience however the emotional strain of loss of peer contact seemed just as severe. Changes over time were also noted as both parental and child experiences were often pertinent to the stage of treatment the child had reached. The approach used in this study allowed for rich and intimate detail about a sensitive issue to be revealed. Such an approach also allowed for the experience of childhood cancer on parents and the children to be more fully realised. Only now can a comprehensive and sensitive medical and psychosocial approach to the child and family be developed. For example, families may benefit from extra support at the time of diagnosis as this was identified as one of the most difficult periods. Parents may also require counselling support in coming to terms with their lack of ability to help their child heal. Given the ease at which children accepted their diagnosis, we need to question whether children are more receptive to adversity. Yet the emotional struggle children battled as a result of their illness also needs to be addressed.