Psychosocial effects of whole-body MRI screening in adult high-risk pathogenic TP53 mutation carriers: a case-controlled study (SIGNIFY).

BACKGROUND: Germline TP53 gene pathogenic variants (pv) cause a very high lifetime risk of developing cancer, almost 100% for women and 75% for men. In the UK, annual MRI breast screening is recommended for female TP53 pv carriers. The SIGNIFY study (Magnetic Resonance Imaging screening in Li Fraumeni syndrome: An exploratory whole body MRI) study reported outcomes of whole-body MRI (WB-MRI) in a cohort of 44 TP53 pv carriers and 44 matched population controls. The results supported the use of a baseline WB-MRI screen in all adult TP53 pv carriers. Here we report the acceptability of WB-MRI screening and effects on psychosocial functioning and health-related quality of life in the short and medium terms. METHODS: Psychosocial and other assessments were carried out at study enrolment, immediately before MRI, before and after MRI results, and at 12, 26 and 52 weeks' follow-up. RESULTS: WB-MRI was found to be acceptable with high levels of satisfaction and low levels of psychological morbidity throughout. Although their mean levels of cancer worry were not high, carriers had significantly more cancer worry at most time-points than controls. They also reported significantly more clinically significant intrusive and avoidant thoughts about cancer than controls at all time-points. There were no clinically significant adverse psychosocial outcomes in either carriers with a history of cancer or in those requiring further investigations. CONCLUSION: WB-MRI screening can be implemented in TP53 pv carriers without adverse psychosocial outcomes in the short and medium terms. A previous cancer diagnosis may predict a better psychosocial outcome. Some carriers seriously underestimate their risk of cancer. Carriers of pv should have access to a clinician to help them develop adaptive strategies to cope with cancer-related concerns and respond to clinically significant depression and/or anxiety.

Psychosocial morbidity in TP53 mutation carriers: is whole-body cancer screening beneficial?

Germline TP53 mutation carriers are at high risk of developing a range of cancers. Effective cancer risk management is an important issue for these individuals. We assessed the psychosocial impact in TP53 mutation carriers of WB-MRI screening as part of the Surveillance in Multi-Organ Cancer (SMOC+) protocol, measuring their unmet needs, anxiety and depression levels as well as cancer worry using psychological questionnaires and in-depth interviews about their experiences of screening. We present preliminary psychosocial findings from 17 participants during their first 12 months on the trial. We found a significant reduction in participants' mean anxiety from baseline to two weeks post WB-MRI (1.2, 95% CI 0.17 to 2.23 p = 0.025), indicative of some benefit. Emerging qualitative themes show most participants are emotionally supported and contained by the screening program and are motivated by their immediate concern about staying alive, despite being informed about the current lack of evidence around efficacy of screening for people with TP53 mutations in terms of cancer morbidity or mortality. For those that do gain emotional reassurance from participating in the screening study, feelings of abandonment by the research team are a risk when the study ends. For others, screening was seen as a burden, consistent with the relentless nature of cancer risk associated with Li-Fraumeni syndrome, though these patients still declared they wished to participate due to their concern with staying alive. Families with TP53 mutations need ongoing support due to the impact on the whole family system. These findings suggest a comprehensive multi-organ screening program for people with TP53 mutations provides psychological benefit independent of an impact on cancer morbidity and mortality associated with the syndrome. The benefits of a multi-organ screening program will be greater still if the screening tests additionally reduce the cancer morbidity and mortality associated with the syndrome. These findings may also inform the care of individuals and families with other multi-organ cancer predisposition syndromes.

Long-Term Worries after Colposcopy: Which Women Are at Increased Risk?

BACKGROUND: A colposcopy examination is the main management option for women with an abnormal cervical screening test result. Although some women experience adverse psychological effects after colposcopy, those at greatest risk are unknown. We investigated predictors of worries about cervical cancer, sex, future fertility and general health during 12 to 30 months after colposcopy. METHODS: We invited 1,515 women, aged 20 to 59 years with low-grade cervical cytology who attended colposcopy to complete questionnaires at recruitment (∼8 weeks after cytology result) and after 12, 18, 24, and 30 months of follow up. Outcomes were worries about having cervical cancer, having sex, future fertility, and general health at any time during follow-up. Factors significantly associated with each outcome were identified using multiple logistic regression. RESULTS: At one or more time points during follow-up, 40% of women reported worries about having cervical cancer, 26% about having sex, 24% about future fertility, and 60% about general health. For all outcomes except sex, worries reported at recruitment were associated with significantly increased risk of worries during follow-up. Significant anxiety at recruitment was associated with all worries during follow-up. Women diagnosed with CIN2+ had significantly higher risks of worries about cervical cancer and future fertility. Management received was associated significantly with worries about cervical cancer and having sex. Younger women significantly more often reported worries about future fertility, whereas women who had children had reduced risk of future fertility worries but increased risk of cervical cancer worries. CONCLUSION: Clinical, sociodemographic, lifestyle, and psychological factors predicted risk of reporting worries after colposcopy.

Women with large (≥3 cm) and locally advanced breast cancers (T3, 4, N1, 2, M0) receiving neoadjuvant chemotherapy (NAC: cyclophosphamide, doxorubicin, docetaxel): addition of capecitabine improves 4-year disease-free survival.

PURPOSE: To determine whether capecitabine (X), combined with docetaxel (T) following doxorubicin (A) and cyclophosphamide (C), enhanced the pathological complete response (pCR) in the breast and axillary lymph nodes (ALNs) of women with large or locally advanced breast cancers (LLABCs) improving outcome, and the effect on quality of life (QoL). PATIENTS AND METHODS: 117 women were enrolled, 112 randomised to 2 cycles of AC (60 mg/m(2), 600 mg/m(2)) given 3 weekly. Tumour responses were assessed by magnetic resonance mammography. Responders (n = 77) received 2 further cycles of AC and were randomised to 4 cycles of T (100 mg/m(2)) (Group A) or T (75 mg/m(2)) and X (2000 mg/m(2)/day), day one to 14 of each 3 weekly cycle (Group B). Non-responders (n = 35) were randomised to 6 cycles of T (Group C) or T + X (Group D). QoL questionnaires were completed at each chemotherapy visit. Pathological responses were evaluated using established criteria. RESULTS: The groups were comparable in patient and tumour characteristics (79.5% T2, 85.7% ductal, 73.2% ER +ve, 22.3% HER2 +ve, 42% involved ALNs). Overall breast pCR was 27.1%, Groups A + C versus B + D (p = 0.446). ALN +ve pCR was 41.9%, Groups A + C versus B + D (p = 0.231). 4-year disease-free survival (DFS) was significantly improved with X (p = 0.016) but not overall survival (p = 0.056). Triple -ve and HER2 +ve tumours, and persistent ALN disease were risk factors for metastases. X increased severe nail changes (p = 0.0002) and hand-foot syndrome (p = 0.014) without affecting QoL. CONCLUSION: NAC-X did not increase breast and ALN pCR but improved 4-year DFS, without detriment to QoL.

The unintended consequences of cervical screening: distress in women undergoing cytologic surveillance.

OBJECTIVE: It is well known that receipt of an initial abnormal cervical cytology test can trigger considerable anxiety among women. Less is known about the impact of follow-up by repeat cytology tests. We quantified prevalence, and identified predictors, of distress after repeat cytologic testing in women with a single low-grade test. METHODS: Within the framework of the TOMBOLA randomized controlled trial of alternative managements, 844 women aged 20 to 59 years with a single routine cytology test showing borderline nuclear abnormalities (BNA; broadly equivalent to atypical squamous cells of undetermined significance) were assigned to follow-up by repeat cytology in primary care (the first test was due 6 months after the initial BNA result). Women completed sociodemographic and psychosocial questionnaires at recruitment and the Impact of Event Scale (IES) 6 weeks after their first follow-up cytology test. Factors associated with significant psychologic distress (IES ≥ 9) were identified using logistic regression. RESULTS: The response rate was 74% (n = 621/844). Of all the respondents, 39% scored in the range for significant distress. Distress varied by follow-up cytology result: negative, 36%; BNA or mild dyskaryosis, 42%; other (including high grade and inadequate), 55%. After adjusting for the cytology result, risk of distress was significantly raised in women who had significant anxiety at recruitment, reported experiencing pain after the follow-up cytology, had children, or were dissatisfied with support they had received after their initial BNA test. CONCLUSIONS: Substantial proportions of women experience surveillance-related psychologic distress after a follow-up cytology test, even when the result is negative. This is an important, albeit unintended, consequence of cervical screening. Strategies to alleviate this distress merit attention.

Measuring the psychosocial burden in women with low-grade abnormal cervical cytology in the TOMBOLA trial: psychometric properties of the Process and Outcome Specific Measure (POSM).

Background: There is a need for an instrument to measure the psychosocial burden of receiving an abnormal cervical cytology result which can be used regardless of the clinical management women receive.Methods: 3331 women completed the POSM as part of baseline psychosocial assessment in a trial of management of low grade cervical cytological abnormalities. Factor analysis and reliability assessment of the POSM were conducted.Results: Two factors were extracted from the POSM: Factor 1, containing items related to worry; and Factor 2 containing items relating to satisfaction with information and support received and change in the way women felt about themselves. Factor 1 had good reliability (Cronbach's alpha 0.769), however reliability of the Factor 2 was poorer(0.482). Data collected at four subsequent time points demonstrated that the factor structure was stable over time.Conclusion: This study demonstrates the presence and reliability of a scale measuring worries within the POSM. This analysis will inform its future use in this population and in other related contexts.

Baseline quality of life factors predict long term survival after elective resection for colorectal cancer.

BACKGROUND: Studies have shown an association between baseline quality of life (Qol) and survival in advanced cancers. The aim of this study was to investigate their predictive value in long term survival after elective colorectal cancer resection. METHODS: A consecutive series of patients undergoing elective colorectal cancer surgery for nonmetastatic disease were recruited in 2003/04. Patients completed standardized quality of life questionnaires (HADS, FACTC, MRS, and PANAS) prior to and 6 weeks after surgery. Univariate (log-rank test) and multivariate analyses (Cox proportional hazards) were performed to predict long term survival. RESULTS: Ninety-seven patients met the inclusion criteria. Sixty-five (67%) were male and the median age of the group was 70 years. Forty-six (47.5%) patients had died and the mean survival was 1,741 days (median 2159, range 9-2923 days). Preoperative mood rating scale and functional assessment of cancer therapy-colorectal FACT C emotional well-being and postoperative FACT C additional concerns were independent predictors of long term survival. CONCLUSION: Incorporating psychosocial measures in preoperative assessment of cancer patients could help to identify patients who require assessment with a view to implementing psychosocial interventions. These active interventions to maximize mood and well-being should form an integral part of multidisciplinary treatment in these patients.

Effects on quality of life, anti-cancer responses, breast conserving surgery and survival with neoadjuvant docetaxel: a randomised study of sequential weekly versus three-weekly docetaxel following neoadjuvant doxorubicin and cyclophosphamide in women with primary breast cancer.

BACKGROUND: Weekly docetaxel has occasionally been used in the neoadjuvant to downstage breast cancer to reduce toxicity and possibly enhance quality of life. However, no studies have compared the standard three weekly regimen to the weekly regimen in terms of quality of life. The primary aim of our study was to compare the effects on QoL of weekly versus 3-weekly sequential neoadjuvant docetaxel. Secondary aims were to determine the clinical and pathological responses, incidence of Breast Conserving Surgery (BCS), Disease Free Survival (DFS) and Overall Survival (OS). METHODS: Eighty-nine patients receiving four cycles of doxorubicin and cyclophosphamide were randomised to receive twelve cycles of weekly docetaxel (33 mg/m2) or four cycles of 3-weekly docetaxel (100 mg/m2). The Functional Assessment of Cancer Therapy-Breast and psychosocial questionnaires were completed. RESULTS: At a median follow-up of 71.5 months, there was no difference in the Trial Outcome Index scores between treatment groups. During weekly docetaxel, patients experienced less constipation, nail problems, neuropathy, tiredness, distress, depressed mood, and unhappiness. There were no differences in overall clinical response (93% vs. 90%), pathological complete response (20% vs. 27%), and breast-conserving surgery (BCS) rates (49% vs. 42%). Disease-free survival and overall survival were similar between treatment groups. CONCLUSIONS: Weekly docetaxel is well-tolerated and has less distressing side-effects, without compromising therapeutic responses, Breast Conserving Surgery (BCS) or survival outcomes in the neoadjuvant setting. TRIAL REGISTRATION: ISRCTN: ISRCTN09184069.

A randomised, controlled trial of the psychological effects of reflexology in early breast cancer.

PURPOSE: To conduct a pragmatic randomised controlled trial (RCT) to evaluate the effects of reflexology on quality of life (QofL) in women with early breast cancer. PATIENTS AND METHODS: One hundred and eighty-three women were randomised 6 weeks post-breast surgery to self-initiated support (SIS) (comparator intervention), SIS plus reflexology, or SIS plus scalp massage (control for physical and social contact). Reflexology and massage comprised eight sessions at weekly intervals. The primary end-point was 18 weeks post surgery; the primary outcome measure was the Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy (FACT-B) - breast cancer version. The secondary end-point was 24 weeks post surgery. Secondary outcome measures were the Hospital Anxiety and Depression Scale (HADS) and the Mood Rating Scale (MRS). RESULTS: At primary end-point, massage, but not reflexology, was significantly better than SIS on the TOI. Reflexology and massage were both better than SIS for MRS relaxation. Massage was better than reflexology and SIS for MRS easygoingness. At secondary end-point, reflexology, but not massage, was better than SIS on the TOI and MRS relaxation. There were no significant differences between reflexology or massage. There were no significant between group differences in HADS anxiety and depression. Self-reported use of out of study complementary therapies indicated that this was unlikely to have a significant effect on findings. CONCLUSIONS: When compared to SIS, reflexology and massage have statistically significant, and, for reflexology, clinically worthwhile, effects on QofL following surgery for early breast carcinoma.

Alterations in the Th1/Th2 balance in breast cancer patients using reflexology and scalp massage.

The diagnosis and treatment of breast cancer can adversely affect quality of life. Here the aim was to determine the effects of reflexology on host defences and endocrine function in women with early breast cancer. Six weeks after surgery for early breast cancer, 183 women were randomly assigned to self-initiated support (SIS), SIS plus foot reflexology, or SIS plus scalp massage. Peripheral blood mononuclear cells and serum were isolated at T1 (6 weeks post surgery; baseline), T2 and T3 (4 and 10 weeks post completion of intervention, respectively). Lymphocyte phenotyping found that CD25(+) cells were significantly higher in the massage group compared with the SIS group at T3. The percentage of T cells, and more specifically the T helper subset expressing IL4, decreased significantly in the massage group compared with the SIS group at T3. This change was accompanied by an increase in the percentage of CD8(+) T cytotoxic cells expressing IFNγ in the massage group. Natural killer and lymphokine activated killer cell cytotoxicity measurements, serum levels of cortisol, prolactin and growth hormone, and flow cytometric assessment of their corresponding receptors all revealed no significant differences between the three groups of patients. This study provides evidence that the immunological balance of patients can be altered in a potentially beneficial manner by massage. The original trial was registered with the International Standard Randomised Controlled Trial Registry (ISRCTN87652313).

Demographic characteristics of patients using a fully integrated psychosocial support service for cancer patients.

BACKGROUND: Psychosocial support services are an important component of modern cancer treatment. A major challenge for all psychosocial services is the achievement of equity of use. Previous studies in the UK have found that women of higher socio-economic status with breast cancer were over-represented amongst those accessing support services. People with other cancer diagnoses, those from socio-economically deprived areas, and men, were under-represented. FINDINGS: The Oncology Health Service, Kingston Upon Hull, UK, delivers fully integrated psychosocial support and interventions. To assess equity of access in this service, a cross-sectional study of all patients with cancer accessing the service during a 5 day period was carried out. One hundred and forty-five patients attended. Forty four percent were male, and the types of cancer were broadly in the proportions expected on the basis of population prevalence (breast cancer 22%, colorectal cancer 21%, lung cancer 16%). Sixty six percent came from the three most deprived quintiles of the Townsend deprivation Index. CONCLUSIONS: The fully integrated Oncology Health Service in Hull is accessed by a more diverse range of patients than previously reported for other services, and is an example of a model of service by which socially equitable use of psychosocial support in the National Health Service might be achieved.

Immuno-modulatory effects of relaxation training and guided imagery in women with locally advanced breast cancer undergoing multimodality therapy: a randomised controlled trial.

Eighty women undergoing multimodality treatment for large (>4cm) or locally advanced (T3, T4, Tx, N2), breast cancers participated in a randomised controlled trial (RCT) to evaluate the immuno-modulatory effects of relaxation training and guided imagery. Patients underwent chemotherapy followed by surgery, radiotherapy, and hormone therapy. Those in the intervention group were taught relaxation and guided imagery. Patients kept diaries of the frequency of relaxation practice and imagery vividness. On 10 occasions during the 37 weeks following the diagnosis, blood was taken for immunological assays CD phenotyping: T cell subsets (helper, cytotoxic), natural killer (NK) and lymphokine activated killer (LAK) cells, B lymphocytes and monocytes; cytotoxicity: NK and LAK cell activities; cytokines interleukin 1 beta (1beta), 2, 4 and 6 and tumour necrosis factor alpha. Significant between-group differences were found in the number of CD25+ (activated T cells) and CD56+ (LAK cell) subsets. The number of CD3+ (mature) T cells was significantly higher following chemotherapy and radiotherapy, in patients randomised to relaxation and guided imagery. Using a median split, women who rated their imagery ratings highly had elevated levels of NK cell activity at the end of chemotherapy and at follow-up. Significant correlations were obtained between imagery ratings and baseline corrected values for NK and LAK cell activity, and IL1beta. Relaxation frequency correlated with the number of CD4+ (T helper) cells, the CD4+:8+ (helper:cytotoxic) ratio, and IL1beta levels. Relaxation training and guided imagery beneficially altered putative anti-cancer host defences during and after multimodality therapy. Such changes, to the best of our knowledge, have not been previously documented in a RCT.

Women who wish breast reconstruction: characteristics, fears, and hopes.

The aims of the present study were to identify the characteristics of a consecutive series of women with newly diagnosed breast cancer and to evaluate the perceived benefits and disadvantages of breast reconstruction. A consecutive series of 125 women completed the Breast Reconstruction Questionnaire, the Hospital Anxiety and Depression Scale, and the Eysenck Personality Questionnaire. The median age was 48 years (range, 28 to 75 years). A total of 49.6 percent (n = 62) indicated that, if it were possible, they would like breast reconstruction. Logistic regression (simultaneous entry) revealed that younger women (p = 0.0001) and more depressed women (p = 0.026) were more likely to wish reconstruction. Marital status, tumor size, extroversion, neuroticism, and tough-mindedness did not independently predict the desire for reconstruction. If given a choice of reconstruction at 3 months or 6 months after mastectomy, of the women who wished reconstruction, 74 percent would prefer it at 3 months. Of the women who wished reconstruction and expressed a preference, 63 percent were afraid reconstruction might mask recurrence, 39 percent were afraid that reconstruction might cause the cancer to return, and 89 percent thought they would be concerned with their appearance after the operation. Positively, 94 percent considered that reconstruction would be beneficial in terms of their self-esteem, 86 percent indicated that reconstruction would give greater freedom to wear any clothing, and 86 percent thought that the cosmetic appearance of breast reconstruction was better than that of a prosthesis. Concerns about recurrence were common. A better understanding of the concerns of women with regard to reconstruction would allow more informed preoperative discussion.

Neoadjuvant docetaxel in breast cancer: 3-year survival results from the Aberdeen trial.

Over the past 30 years there has been an increased use of neoadjuvant (or primary) chemotherapy for treating patients with breast cancer. However, while it is clear that chemotherapy given in the adjuvant setting after surgery does prolong patients' overall and disease-free survival, the evidence that chemotherapy in the neoadjuvant setting also increases survival remains unproven. In the Aberdeen study, 162 patients with large and locally advanced breast cancer underwent 4 cycles of CVAP (cyclophosphamide/vincristine/doxorubicin/prednisone) primary chemotherapy. Patients with a complete or partial response were then randomized to either 4 further cycles of CVAP or 4 cycles of docetaxel (100 mg/m2). It was shown that the addition of sequential docetaxel (100 mg/m2) to CVAP neoadjuvant chemotherapy resulted in a significantly enhanced clinical response rate (94% vs. 64%) and a substantially increased complete histopathological response rate (34% vs. 16%) when compared to patients receiving CVAP alone. Furthermore, patients receiving docetaxel had an increased breast conservation rate (67% vs. 48%) and an increased survival at a median follow-up of 3 years. It is important to note that this was a small study, and the survival results should be interpreted with caution. The results are encouraging, however, and further studies are urgently required.

Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel.

PURPOSE: To compare the efficacy of neoadjuvant (NA) docetaxel (DOC) with anthracycline-based therapy and determine the efficacy of NA DOC in patients with breast cancer initially failing to respond to anthracycline-based NA chemotherapy (CT). PATIENTS AND METHODS: Patients with large or locally advanced breast cancer received four pulses of cyclophosphamide 1,000 mg/m(2), doxorubicin 50 mg/m(2), vincristine 1.5 mg/m(2), and prednisolone 40 mg (4 x CVAP) for 5 days. Clinical tumor response was assessed. Those who responded (complete response [CR] or partial response [PR]) were randomized to receive further 4 x CVAP or 4 x DOC (100 mg/m(2)). All nonresponders received 4 x DOC. RESULTS: One hundred sixty-two patients were enrolled; 145 patients completed eight cycles of NA CT. One hundred two patients (66%) achieved a clinical response (PR or CR) after 4 x CVAP. After randomization, 50 patients received 4 x CVAP and 47 patients received 4 x DOC. In patients who received eight cycles of CT, the clinical CR (cCR) and clinical PR (cPR) (94% v 66%) and pathologic CR (pCR) (34% v 16%) response rates were higher (P =.001 and P =.04) in those who received further DOC. Intention-to-treat analysis demonstrated cCR and cPR (85% v 64%; P =.03) and pCR (31% v 15%; P =.06). Axillary lymph node examination revealed residual tumor in 33% of patients who received 8 x CVAP and 38% of patients who received further DOC. In patients who failed to respond to the initial CVAP, 4 x DOC resulted in a cCR and cPR rate of 55% and a pCR rate of 2%. Forty-four percent of these patients had residual tumor within axillary lymph nodes. CONCLUSION: NA DOC resulted in substantial improvement in responses to DOC.

A comparison of real patients, simulated patients and videotaped interview in teaching medical students about alcohol misuse.

Doctors perform poorly in identifying and in treating patients with alcohol misuse problems and this has been linked to inadequate undergraduate education. We compared three methods of teaching among Aberdeen medical students. In groups of eight or nine students, teaching was conducted with a simulated patient, with real patients or with a videotaped interview. The teachers were five consultant psychiatrists. At the end of each teaching session, students completed a measure of knowledge (multiple-choice questions), two measures of attitudes towards alcohol misusers and a questionnaire tailored to assessment of the teaching session. From the class of 176 students, 156 (89%) participated in the study. Two-way analyses of variance identified a significant difference between teaching methods; students rated the simulated patient sessions as more helpful in acquiring interview skills (F = 11.71, df 2, p < 0.001). We have since expanded our use of simulated patients in the undergraduate teaching programme.