Managing the consequences of cancer treatment and the English National Cancer Survivorship Initiative.

BACKGROUND: In 2007 the English National Cancer Survivorship initiative was launched as a partnership between a national charity, Macmillan Cancer Support, the English Department of Health (DH) and the quality improvement agency NHS Improvement. The initiative involved a number of work streams, one of which was to improve the detection and management of the Consequences of adult cancer Treatment (COT). MATERIAL AND METHODS: The adult COT group took evidence from a range of stakeholders and published a vision and work programme focused on awareness raising, linking self- administered questionnaires to routine activity data collection and testing new models of care with a particular focus on pelvic cancers. RESULTS: Key outputs include national media campaigns, publications demonstrating the value of linking cancer treatment episodes to routine recording of chronic illness, identification of sensitive Patient Reported Outcome Measures (PROMs) items for use in national surveys, evidence reviews and published national guidelines, together with the development of a three level risk stratified model of care. Pilot testing with survivors treated for pelvic cancers, and adult survivors with radiation-induced brachial plexopathy has been completed. CONCLUSION: Early results suggest that a systematic approach to the prevention, detection and management of some treatment-related consequences can significantly improve the ability of patients to manage their conditions. As a result of these findings, new services have now been commissioned by the NHS, initially for those with complex problems.

Use of prenatal chromosomal microarray: prospective cohort study and systematic review and meta-analysis.

OBJECTIVES: Chromosomal microarray analysis (CMA) is utilized in prenatal diagnosis to detect chromosomal abnormalities not visible by conventional karyotyping. A prospective cohort of women undergoing fetal CMA and karyotyping following abnormal prenatal ultrasound findings is presented in the context of a systematic review and meta-analysis of the literature describing detection rates by CMA and karyotyping. METHODS: We performed a prospective cohort study of 243 women undergoing CMA alongside karyotyping when a structural abnormality was detected on prenatal ultrasound. A systematic review of the literature was also performed. MEDLINE (1970-Dec 2012), EMBASE (1980-Dec 2012) and CINAHL (1982-June 2012) databases were searched electronically. Selected studies included > 10 cases and prenatal CMA in addition to karyotyping. The search yielded 560 citations. Full papers were retrieved for 86, and 25 primary studies were included in the systematic review. RESULTS: Our cohort study found an excess detection rate of abnormalities by CMA of 4.1% over conventional karyotyping when the clinical indication for testing was an abnormal fetal ultrasound finding; this was lower than the detection rate of 10% (95% CI, 8-13%) by meta-analysis. The rate of detection for variants of unknown significance (VOUS) was 2.1% (95% CI, 1.3-3.3%) when the indication for CMA was an abnormal scan finding. The VOUS detection rate was lower (1.4%; 95% CI, 0.5-3.7%) when any indication for prenatal CMA was meta-analyzed. CONCLUSION: We present evidence for a higher detection rate by CMA than by karyotyping not just in the case of abnormal ultrasound findings but also in cases of other indications for invasive testing. It is likely that CMA will replace karyotyping in high-risk pregnancies.

The health and well-being of cancer survivors in the UK: findings from a population-based survey.

BACKGROUND: To compare self-reported health and well-being in a sample of cancer survivors with individuals who have not had cancer and with individuals who have a serious chronic condition other than cancer. PATIENTS AND METHODS: A cross-sectional survey drawn from an online panel of 400,000 UK citizens supplemented with other online recruitment and telephone recruitment. The participants were 4892 individuals 30 years of age or above, including 780 individuals with a previous cancer diagnosis, 1372 individuals with one or more of 10 chronic conditions but not cancer and 2740 individuals without a previous cancer diagnosis or chronic condition. Thirteen measures of health and well-being were constructed from answers to 25 survey items covering physical, psychological and social dimensions of health and well-being. RESULTS: Cancer survivors were significantly more likely to report poor health outcomes across all 13 measures than those with no history of cancer or a chronic condition. The adjusted odds ratios for cancer survivors with no chronic conditions compared with healthy participants ranged from 1.37 (95% confidence interval (CI): 1.31-1.96) for emotional well-being to 3.34 (95% CI: 2.74-4.08) for number of health professionals consulted in the last 12 months. The health profile of cancer survivors was similar to those with a history of a serious chronic health condition. CONCLUSIONS: A substantial number of individuals who have had a diagnosis of cancer experience ongoing poor health and well-being following cancer and cancer treatment. The results of this study provide an initial basis for the development of specific help and support for cancer survivors.

Patterns of complementary and alternative medicine use among patients undergoing cancer treatment.

This study aimed to assess the prevalence of complementary and alternative medicine (CAM) use in a representative cancer population prior to and within 6 months of diagnosis. A total of 304 newly diagnosed cancer patients from two UK cancer centres completed a postal survey. Of them, 100 patients (32.9%) used CAM before their cancer diagnosis, 59 of these CAM users continued post diagnosis. Twenty-nine individuals who had not used CAM before began to use it after their cancer diagnosis, creating a total of 88 (28.9%) CAM users in this sample. Reasons for not using CAM included lack of interest, lack of information or endorsement from professionals and satisfaction with conventional care. For those using CAM before diagnosis but not afterwards, the most common reason was a lack of expert guidance on what was safe to use. The use of CAM medicines bought from health food and other retail outlets was high. Complementary and alternative medicine use in cancer patients is common and demonstrates a complex pattern, but CAM use is not significantly greater than in the general population. Some patients purchase CAM medicines without seeking medical advice, thus risking drug interactions. Research to generate information on safety and efficacy of CAM is required.

Survivorship, late effects and cancer of the cervix.

As the prevention and treatment of cervical cancer improves, there is increasing focus on the months and years after cancer treatment. Of those women living after a diagnosis of cancer, 10% will have a gynaecological malignancy and although the incidence of cervix cancer has dropped over the last 20 years, so has the age at diagnosis, with more than 60% surviving at least 5 years. In a recent report, 63% of 231 064 US survivors of cervix cancer were more than 10 years from diagnosis. More survivors are living long enough to develop chronic treatment-related conditions. The 2007 English Cancer Reform Strategy highlighted the importance of cancer survivorship and uses the US National Coalition for Cancer Survivorship definition-'living through and beyond cancer'. The emerging picture is of populations living after a diagnosis of cancer without active disease, still having similar health and disability profiles to populations with a diagnosis of a chronic illness. This offers new challenges in identifying and meeting their needs.

An integrated support and information centre in a large U.K. Cancer Centre established in 1993 and replicated in more than 60 units across the United Kingdom and Australia.

Established in 1993 after a 2-year consultation between professionals and cancer patients, the Lynda Jackson Macmillan Centre (LJMC) has been a catalyst for change in the United Kingdom. The Centre began with a small core staff in a purpose-built building next to a cancer centre, networking with outreach workers in 12 surrounding hospitals, with a mission to improve information, communication, and support for cancer patients. Since 1996, the LJMC model has been adopted and developed by the charity Macmillan Cancer Support and has been spread to more than 60 units across the United Kingdom and Australia.Introducing complementary therapies (CAMS) to a cancer centre was a particular early challenge. Establishing a shared understanding of the role of complementary therapies and developing nationally accredited written information about them, credible recruitment and governance procedures for therapy practitioners, agreed outcome measures, and peer-reviewed evaluation and research have all been important in engaging cancer physicians and managers; however, charitable funding is still required to support free access to most complementary therapies.An integrated supportive care service for cancer patients begins with a shift in the culture of cancer treatment organizations, moving from a professional-centred to a patient-centred agenda. Real reach and impact requires "new" ideas and services to be integrated into the routine practice of the cancer care delivery organizations. A key lesson learned over the last 15 years is that an integrated support centre must continually adapt to be viable. Sustaining meaningful user guidance is a particular challenge. Support for self-management and the testing and development of CAM services are growing parts of the portfolio.

Fetal Dysmorphology-Still an Essential Art. Analysis of the Limitations of Microarray in a Fetal Population and a Look Toward the Genome Sequencing Era.

Cytogenomic microarray allows assessment of the genome at higher resolutions than traditional karyotyping. The objective of this study is to evaluate the utility of microarray in a routine fetal autopsy setting before the advent of routine fetal exome/genome sequencing and the issues these technologies may generate. A systematic review of fetal postmortems at 12-24 weeks gestation between January 2011 and December 2014 was undertaken. Cases where there was no consent for audit, research, or genetic testing were excluded as were cases referred to the Procurator Fiscal, stillbirths, and neonatal deaths. Copy number variations were detected in 16 cases. In addition, there was 1 case of uniparental disomy; not all of these were related to the phenotype. There were a number of cases with phenotypic abnormalities and normal array results. Five of these underwent directed mutation analysis-3 were positive. Genetic laboratory investigations such as microarray and Quantitative Fluorescent-Polymerase Chain Reaction may increase the diagnostic yield in the assessment of fetal dysmorphology. However, this study shows that genetic results not only require careful review given the potential uncertain significance but also require phenotypic assessment of the fetus by a competent fetal dysmorphologist to determine the likely causative effect of any detected anomaly. This best practice will also extend to next generation sequencing and interpretation of variants of unknown significance. Fetal medicine teams should ideally include specialists well versed in assessment of fetal anomaly to provide families with the best possible information about the cause of their pregnancy loss and their options for future pregnancies.

The place of radiotherapy in stage I and IIA Hodgkin's disease (or radiotherapy revisited).

For the majority of patients presenting with early Hodgkin's disease, the chance of death due to their disease is related to prognostic factors, e.g. age, systemic symptoms, ESR bulk, number of sites of disease, histology, haemoglobin, lymphocyte count etc. More than 50% of those with Stage I and IIA disease fall into an intermediate prognostic category where a variety of initial treatment strategies--chemotherapy alone (CT), radiotherapy alone (RT) or a combination of chemotherapy and radiotherapy (combined modality therapy CMT) result in comparable survival rates. There is therefore increasing emphasis on incidence of relapse and treatment related morbidities rather than on survival alone when evaluating the role of different treatment for Hodgkin's disease. Radiotherapy has an essential part to play in any initial strategy aiming to keep relapse rate low, as chemotherapy alone has been demonstrated to be less effective in treating macroscopic disease. Late side-effects associated with radiation are largely associated with obsolete techniques involving very wide fields, high doses and large fraction size delivered to anterior structures within the thorax. The risk of second solid tumour appears related to the volume of radiation fields and the risk of cardiac damage is probably related to both total dose and dose per fraction delivered. There is still uncertainty as to the potential late toxicity of modern techniques, particularly in combination with chemotherapy. Increasingly numbers of patients are likely to be treated with initial CMT rather than RT alone to reduce relapse rates. The risk of leukaemia associated with CMT to patients with curable Hodgkin's disease appears to have been overestimated.(ABSTRACT TRUNCATED AT 250 WORDS)

Development and clinical application of an innovative fluorescence in situ hybridization technique which detects submicroscopic rearrangements involving telomeres.

We report an innovative fluorescence in situ hybridization technique which exploits a unique resource of 41 telomere-specific probes and allows the simultaneous analysis of the subtelomeric region of every chromosome for deletion, triplication and balanced translocation events. This technique requires only a single microscope slide per patient and is expected to be a useful diagnostic tool with applications in the fields of idiopathic mental retardation, the detection of congenital abnormalities and in some forms of cancer. This will lead to more accurate genetic counselling of patients and their families and will provide the basis for future diagnostic, therapeutic and preventative measures.

A 12 country field study of the EORTC QLQ-C30 (version 3.0) and the head and neck cancer specific module (EORTC QLQ-H&N35) in head and neck patients. EORTC Quality of Life Group.

This study tests the reliability and validity of the European Organization for Research and Treatment of Cancer (EORTC) head and neck cancer module (QLQ-H&N35) and version 3.0 of the EORTC Core Questionnaire (QLQ-C30) in 622 head and neck cancer patients from 12 countries. The patients completed the QLQ-C30, the QLQ-H&N35 and a debriefing questionnaire before antineoplastic treatment or at a follow-up. 232 patients receiving treatment completed a second questionnaire after treatment. Compliance was high and the questionnaire was well accepted by the patients. Multitrait scaling analysis confirmed the proposed scale structure of the QLQ-H&N35. The QLQ-H&N35 was responsive to differences between disease status, site and patients with different Karnofsky performance status, and to changes over time. The new physical functioning scale (with a four-point response format) of version 3.0 of the QLQ-C30 was shown to be more reliable than previous versions. Thus, the QLQ-H&N35, in conjunction with the QLQ-C30, appears to be reliable, valid and applicable to broad multicultural samples of head and neck cancer patients.

The influence of national attitudes on the use of radiotherapy in advanced and metastatic cancer, with particular reference to differences between the United Kingdom and the United States of America: implications for future studies.

Recent publications have suggested significant variation in dose and number of fractions of radiotherapy given to palliate advanced and metastatic cancer. Four types of published study are considered: multicenter trials, retrospective studies, patterns of care studies, and surrogate studies. These suggest that there are significant differences in the characteristics of patients considered incurable, the aims and expectations of palliative treatment, the predicted survival of patients treated palliatively, and the influence of clinical trials. Future studies are proposed to confirm such variation.

Treatment strategies in advanced and metastatic cancer: differences in attitude between the USA, Canada and Europe.

Six-hundred and forty four radiation therapists from 21 European countries, Canada, and the USA responded to a questionnaire regarding the management of three cases of advanced cancer. The cases were a 64-year-old man with brain metastases from small cell carcinoma of the lung; a 64-year-old woman with bone metastases from carcinoma of the breast and a 59-year-old man with squamous cell carcinoma of the bronchus and mediastinal nodes. There was variation as to the perceived prognosis and appropriate aims of therapy, particularly for the case of squamous cell carcinoma of the bronchus. The total dose and number of fractions could be related to the perceived aims and expectations of treatment, for example, those aiming to extend life gave higher doses of radiotherapy and those aiming only to relieve symptoms gave lower. Similarly, those describing treatment as radical and estimating longer survival gave higher doses and more fractions than those treating palliatively. Variations in the role of the radiation oncologist in the management of advanced and metastatic cancer in the USA, Canada and Europe are discussed.

Continuous hyperfractionated accelerated radiotherapy in locally advanced carcinoma of the head and neck region.

Shortening of the overall duration of radiotherapy would reduce the possibility repopulation of tumor during treatment. Most clinical trials of such accelerated radiotherapy have incorporated a split course to improve normal tissue tolerance. Any interruption, however, even for the week-end, may allow repopulation to occur. A scheme of radiotherapy has been used during which treatment was given 3 times per day on each of 12 consecutive days without interruption for the week-end. In a pilot study a significant improvement in survival and local tumor control has been achieved in 48 patients with head and neck tumors when comparison was made with a previously treated group. A randomized controlled clinical trial is planned.

Experience with CHART.

Continuous, hyperfractionated, accelerated radiotherapy (CHART) has been used at the Mount Vernon Cancer Treatment Center since January 1985. Patients with head and neck tumors and those with locally advanced non-oat cell carcinoma of the bronchus have formed the large majority of the 263 patients treated. Early reactions in the mucosae of the mouth and pharynx have been pronounced, but all have healed, while those in the skin have been less severe than with conventional radiotherapy. An unexpected late morbidity was radiation myelitis in four patients, but in other tissues including the skin, mucosae, the connective tissues, and the salivary glands, late changes appear reduced compared to those after conventional radiotherapy. In 92 patients with squamous cell carcinoma of the major sites in the head and neck region, of whom 71 were in Stages T3 and T4, a complete regression at the primary site and nodes was achieved in 90%. This can be compared with 62% in similar patients previously treated with curative intent at Mount Vernon between 1980 and 1985; the difference was maintained in follow-up (p = 0.003). Of 76 assessable patients with non-oat cell carcinoma of the bronchus, a complete radiological response has been achieved in 40%, compared to 12% in a retrospective group; again the difference has been maintained in follow up (p = 0.0001). A 1-year survival of 60% can be compared to 40% in the retrospective group and a 2-year survival of 29% compared to 12% (p = 0.01). With a reduction of permitted dose to the spinal cord, CHART gives promise for improvement in tumor control and a reduction in late morbidity. These promising results have led to multi-center randomized controlled clinical trials in carcinoma at the head and neck and in non-oat cell carcinoma of the bronchus. In these studies, CHART is being compared with conventional fractionated radiotherapy.

Treatment strategies for advanced and metastatic cancer in Europe.

ESTRO members were surveyed by questionnaires regarding the management of three cases of advanced cancer and the organisation of cancer care in their centre. There were 278 replies from within Europe from a total of 21 countries and 231 centres. The cases were a 64-year-old man with brain metastases from a small cell carcinoma of the lung, a 64-year-old woman with bone metastases from carcinoma of the breast on tamoxifen and a 59-year-old man with a squamous cell carcinoma (NSCLC) of the bronchus and positive mediastinal lymph nodes. Over 90% of respondents replied that they would give radiotherapy in each of these cases. The median total doses were 30 Gy for the brain metastases, 30 Gy for the bony metastases and 56 Gy for the case of NSCLC. There was variation as to the perceived prognosis and appropriate aims of therapy, particularly for the case of NSCLC. The total dose and number of fractions of radiotherapy could be related to the perceived aims and expectations of treatment, e.g. those aiming to extend life gave significantly higher total doses of radiotherapy (p = 0.0001) and those aiming to relieve symptoms gave significantly lower total doses (p = 0.0001). Treatment for this case was described as "radical" by 53% of respondents and as "palliative" by 47% and the prognosis was estimated to be less than 12 months by 41% and 1-2 years by 44%. Those describing treatment as radical and estimating longer survival gave higher doses and more fractions than those treating palliatively.(ABSTRACT TRUNCATED AT 250 WORDS)

How useful are observational reports in the evaluation of interventions for radiation morbidity?: an analysis of formalin therapy for late radiation proctitis.

BACKGROUND AND PURPOSE: Evidence-based medicine requires the systematic and critical evaluation of published and unpublished trials. Problems arise when a clinical condition is relatively rare and the only available data relate to experiential knowledge. The way forward would be to recommend the development of good quality randomized controlled studies. Until then, we are left with the situation where some information exists, albeit in the form of case reports and small series. Should this information be used and what features would determine its strength? METHODS: Using the example of formalin therapy in haemorrhagic radiation proctitis, a treatment for a rare condition, we were able to identify 16 published studies, 13 of which were retrospective and three of which were prospective. The quality of reporting detail was assessed by comparison to the features in a 'proposed minimum dataset' for an uncontrolled study addressing this topic. RESULTS: The mean score for quality of reporting detail for these studies was 50.6% (range 25-70%). Earlier studies reported a significantly higher response rate than subsequent studies and although there was a tendency for smaller studies to report higher response rates, this was not significant. The score for detail of reporting did not improve with year of publication and the correlation between the size of the study and the detail of reporting was not statistically significant. CONCLUSIONS: The information presented is of exceedingly variable quality. If these studies are to be used, where insufficient controlled trials are available, they should be scored for methodology, and these scores used to assist interpretation of results. This would be facilitated if an accepted reporting format including specific criteria was available.

Variation in mantle technique: implications for establishing priorities for quality assurance in clinical trials.

74 European and American radiotherapists responded to a questionnaire investigating the treatment of a patient with stage IIA non-bulky Hodgkin's disease by mantle irradiation. A consensus was present for the dose aims to involved and uninvolved lymph nodes and the acceptable incidence of late normal tissue effects. There was less agreement as to the total dose and dose per fraction required to maintain normal tissue toxicity within the agreed acceptable incidence. Variation was found in the radiation technique employed, the amount of spinal cord shielding used, the prescription point, modifications if irradiation was given after chemotherapy, and the routine recording of dose and dose per fraction to the normal tissue at risk. This descriptive survey confirms the need for well designed quality assurance programmes and indicates the areas of particular uncertainty that currently exist.

Near-haploid cell line in megakaryoblastic transformation of Philadelphia-positive chronic myeloid leukemia.

A case of near haploidy in a patient with an acute megakaryoblastic transformation of Philadelphia (Ph)-positive chronic myeloid leukemia (CML) was studied. Cytogenetic studies revealed persistence of a Ph-positive pseudodiploid cell line and the emergence of a Ph-positive near-haploid cell line, i.e., 46,XX,t(9;22)(q34;q11)/28,XX,t(9;22),+8,+14,+18,+29. The near-haploid cell line is a rare cytogenetic finding. The patient rapidly deteriorated and died.

Interventions for the physical aspects of sexual dysfunction in women following pelvic radiotherapy.

BACKGROUND: Following pelvic radiotherapy (RT), a proportion of women experience problems related to sexual function, which are multifactorial in origin. The physical components relate to distortion of the perineum and vagina, which may occur as a result of surgery and/or radiotherapy and compromise sexual activity resulting in considerable distress. OBJECTIVES: The aim of this review was to evaluate the evidence for treatment options addressing the physical components of sexual dysfunction arising from pelvic radiotherapy as prevention or treatment of acute or late complications. SEARCH STRATEGY: The concepts used included synonyms for radiation therapy and brachytherapy and synonyms for the spectrum of physical aspects of sexual dysfunction in women. randomized. We searched the Cochrane Controlled Trials Register (CENTRAL), issue 1, 2002, MEDLINE 1966 to 2002, EMBASE 1980 to 2002, CANCERCD 1980 to 2002, Science Citation Index 1991 to 2002, CINAHL 1982 to 2002, as well as sources of grey literature. We also hand searched relevant textbooks and contacted experts in the field. SELECTION CRITERIA: Any study describing the therapeutic trial of a treatment to relieve the physical aspects of female sexual dysfunction which had developed following pelvic radiotherapy was considered. The quality of each study was then assessed by two reviewers independently to determine its suitability for inclusion in statistical analysis. DATA COLLECTION AND ANALYSIS: Thirty-two references met the inclusion criteria for the search but of these only four were suitable to be included for statistical analysis. MAIN RESULTS: The strongest evidence for benefit is the grade IC data in the topical oestrogens and benzydamine sections which describes the treatment of acute radiation vaginal changes. The use of vaginal dilators to prevent the development of vaginal stenosis is supported by grade IIC evidence. The value of hyperbaric oxygen therapy and surgical reconstruction is supported by the much weaker grade IIIC evidence in the form of case series. REVIEWER'S CONCLUSIONS: These findings reflect the quality of published data regarding interventions for this aspect of the management of radiation induced complications. Although there is grade IC evidence, these studies are not recent, the allocation concealment is unclear in the text, and overall there is a variable level of assessment of the response, emphasising the need for more studies to be conducted with improved designs to clarify the investigative process and support the final result.