• Aberrant CDKN1A transcriptional response associates with abnormal sensitivity to radiation treatment.

      Badie, Christophe; Dziwura, S; Raffy, C; Tsigani, Theodora; Alsbeih, G; Moody, J; Finnon, Paul; Levine, Edward; Scott, David A; Bouffler, Simon; et al. (2008-06-03)
      Normal tissue reactions to radiation therapy vary in severity among patients and cannot be accurately predicted, limiting treatment doses. The existence of heritable radiosensitivity syndromes suggests that normal tissue reaction severity is determined, at least in part, by genetic factors and these may be revealed by differences in gene expression. To test this hypothesis, peripheral blood lymphocyte cultures from 22 breast cancer patients with either minimal (11) or very severe acute skin reactions (11) have been used to analyse gene expression. Basal and post-irradiation expression of four radiation-responsive genes (CDKN1A, GADD45A, CCNB1, and BBC3) was determined by quantitative real-time PCR in T-cell cultures established from the two patient groups before radiotherapy. Relative expression levels of BBC3, CCNB1, and GADD45A 2 h following 2 Gy X-rays did not discriminate between groups. However, post-irradiation expression response was significantly reduced for CDKN1A (P<0.002) in severe reactors compared to normal. Prediction of reaction severity of approximately 91% of individuals sampled was achieved using this end point. Analysis of TP53 Arg72Pro and CDKN1A Ser31Arg single nucleotide polymorphisms did not show any significant association with reaction sensitivity. Although these results require confirmation and extension, this study demonstrates the possibility of predicting the severity of acute skin radiation toxicity in simple tests.
    • Effectiveness of a home care nursing program in the symptom management of patients with colorectal and breast cancer receiving oral chemotherapy: a randomized, controlled trial.

      Molassiotis, Alexander; Brearley, Sarah; Saunders, Mark P; Craven, Olive; Wardley, Andrew M; Farrell, Carole; Swindell, Ric; Todd, Chris; Luker, Karen; University of Manchester, School of Nursing, University Place, Manchester, M13 9PL, United Kingdom. alex.molassiotis@manchester.ac.uk (2009-12-20)
      PURPOSE: To assess the effectiveness of a symptom-focused home care program in patients with cancer who were receiving oral chemotherapy in relation to toxicity levels, anxiety, depression, quality of life, and service utilization. PATIENTS AND METHODS: A randomized, controlled trial was carried out with 164 patients with a diagnosis of colorectal (n = 110) and breast (n = 54) cancers who were receiving oral capecitabine. Patients were randomly assigned to receive either a home care program by a nurse or standard care for 18 weeks (ie, six cycles of chemotherapy). Toxicity assessments were carried out weekly for the duration of the patients' participation in the trial, and validated self-report tools assessed anxiety, depression, and quality of life. RESULTS: Significant improvements were observed in the home care group in relation to the symptoms of oral mucositis, diarrhea, constipation, nausea, pain, fatigue (first four cycles), and insomnia (all P < .05). This improvement was most significant during the initial two cycles. Unplanned service utilization, particularly the number of inpatient days (57 v 167 days; P = .02), also was lower in the home care group. CONCLUSION: A symptom-focused home care program was able to assist patients to manage their treatment adverse effects more effectively than standard care. It is imperative that patients receiving oral chemotherapy are supported with such programs, particularly during initial treatment cycles, to improve their treatment and symptom experiences.
    • Inter-fraction motion and dosimetric consequences during breast intensity-modulated radiotherapy (IMRT).

      Jain, Pooja; Marchant, Thomas E; Green, Melanie M; Watkins, Gillian R; Davies, Julie; McCarthy, Claire; Loncaster, Juliette A; Stewart, Alan L; Magee, Brian; Moore, Christopher J; et al. (2009-01)
      BACKGROUND AND PURPOSE: Intensity-modulated radiotherapy (IMRT) can improve dose homogeneity within the breast planned target volume (PTV), but may be more susceptible to patient/organ motion than standard tangential radiotherapy (RT). We used daily cone-beam CT (CBCT) imaging to assess inter-fraction motion during breast IMRT and its subsequent impact on IMRT and standard RT dose homogeneity. MATERIALS AND METHODS: Ten breast cancer patients selected for IMRT were studied. CBCT images were acquired immediately after daily treatment. Automatic image co-registration was used to determine patient positioning variations. Daily PTV contours were used to calculate PTV variations and daily delivered IMRT and theoretically planned tangential RT dose. RESULTS: Group systematic (and random) setup errors detected by CBCT were 5.7 (3.9)mm laterally, 2.8 (3.5)mm vertically and 2.3 (3.2)mm longitudinally. Rotations >2 degrees in any axis occurred on 53/106 (50%) occasions. Daily PTV volume varied up to 23%. IMRT dose homogeneity was superior at planning and throughout the treatment compared with standard RT (1.8% vs. 15.8% PTV received >105% planned mean dose), despite increased motion sensitivity. CONCLUSIONS: CBCT revealed inadequacies of current patient positioning and verification procedures during breast RT and confirmed improved dose homogeneity using IMRT for the patients studied.
    • Lymphocyte telomere length correlates with in vitro radiosensitivity in breast cancer cases but is not predictive of acute normal tissue reactions to radiotherapy.

      Iwasaki, Toshiyasu; Robertson, Naomi; Tsigani, Theodora; Finnon, Paul; Scott, David A; Levine, Edward; Badie, Christophe; Bouffler, Simon; Radiation Effects Department, Health Protection Agency, Centre for Radiation, Chemical and Environmental Hazards, Radiation Protection Division, Chilton, Didcot, Oxfordshire, UK. (2008-04)
      PURPOSE: To examine the hypothesis that lymphocyte telomere length may be predictive of both breast cancer susceptibility and severity of acute reactions to radiotherapy. MATERIALS AND METHODS: Peripheral blood lymphocyte cultures from breast cancer patients (with normal or severe skin reactions to radiotherapy) and normal individuals were assessed for in vitro radiosensitivity as measured by apoptosis, cell cycle delay and cytotoxicity. Telomere lengths were determined by a flow cytometric fluorescence in situ hybridization assay (FLOW-FISH). RESULTS: Female breast cancer cases (n = 24) had reduced lymphocyte telomere lengths by comparison with healthy controls (n = 20, p < 0.04). However, the average age of healthy controls was less (45.4) than cases (53). When the control group was modified to give a better age match (51.5, n = 13) the reduced telomere length in cases was not significantly different from controls. Lymphocytes from breast cancer cases also showed reduced cell cycle delay (p < 0.001) and increased apoptosis (p < 0.01) following irradiation in vitro at 3 and 5 Gy respectively, compared to healthy controls. Statistical significance was maintained with the improved age matching of groups. Comparison of lymphocytes from breast cancer patients with normal (n = 11) and severe (n = 13) skin reactions to radiotherapy failed to identify differences in telomere length or cellular radiosensitivity in this limited sample. CONCLUSIONS: This study adds to the evidence suggesting a correlation between altered cellular radiosensitivity and breast cancer. However, in the cases investigated, telomere length does not appear to be predictive of acute skin reactions to radiotherapy.
    • Psoas abscess: an unusual presentation of a metastatic breast cancer after 25 years.

      Satpathy, Anjana; Burt, Paul A; Guy, Andrew J; Department of General Surgery, Leighton Hospital, Crewe, UK. anjana_satpathy@yahoo.co.uk (2009-04-01)
    • The UK national breast cancer screening programme for survivors of Hodgkin lymphoma detects breast cancer at an early stage.

      Howell, Sacha J; Searle, C; Goode, Valerie; Gardener, T; Linton, Kim M; Cowan, Richard A; Harris, Maggie A; Hopwood, Penelope; Swindell, Ric; Norman, Alison; et al. (2009-08-18)
      BACKGROUND: Supradiaphragmatic radiotherapy (SRT) to treat Hodgkin's lymphoma (HL) at a young age increases the risk of breast cancer (BC). A national notification risk assessment and screening programme (NRASP) for women who were treated with SRT before the age of 36 years was instituted in the United Kingdom in 2003. In this study, we report the implementation and screening results from the largest English Cancer Network. METHODS: A total of 417 eligible women were identified through cancer registry/hospital databases and from follow-up (FU) clinics. Screening results were collated retrospectively, and registry searches were used to capture BC cases. RESULTS: Of the 417 women invited for clinical review, 243 (58%) attended. Of these 417 women, 23 (5.5%) have been diagnosed with BC, a standardised incidence ratio of 2.9 compared with the age-matched general population. Of five invasive BCs diagnosed within the NRASP, none involved axillary lymph nodes compared with 7 of 13 (54%) diagnosed outside the programme (P<0.10). The mean latency for BC cases was 19.5+/-8.35 years and the mean FU duration for those unaffected by BC was 14.6+/-9.11 years (P<0.01), suggesting that those unaffected by BC remain at high risk. Recall and negative biopsy rates were acceptable (10.5 and 0.8%, respectively). CONCLUSIONS: The NRASP appears to detect BC at an early stage with acceptable biopsy rates, although numbers are small. Determination of NRASP results on a national basis is required for the accurate evaluation of screening efficacy in women previously treated with SRT.