Paul Symonds

Depression and anxiety in long-term cancer survivors compared with spouses and healthy controls: a systematic review and meta-analysis

BACKGROUNDnCancer survival has improved in the past 20 years, affecting the long-term risk of mood disorders. We assessed whether depression and anxiety are more common in long-term survivors of cancer compared with their spouses and with healthy controls.nnnMETHODSnWe systematically searched Medline, PsycINFO, Embase, Science Direct, Ingenta Select, Ovid, and Wiley Interscience for reports about the prevalence of mood disorders in patients diagnosed with cancer at least 2 years previously. We also searched the records of the International Psycho-oncology Society and for reports that cited relevant references. Three investigators independently extracted primary data. We did a random-effects meta-analysis of the prevalences of depression and anxiety in cancer patients compared with spouses and healthy controls.nnnFINDINGSnOur search returned 144 results, 43 were included in the main analysis: for comparisons with healthy controls, 16 assessed depression and ten assessed anxiety; of the comparisons with spouses, 12 assessed depression and five assessed anxiety. The prevalence of depression was 11·6% (95% CI 7·7-16·2) in the pooled sample of 51u2008381 cancer survivors and 10·2% (8·0-12·6) in 217u2008630 healthy controls (pooled relative risk [RR] 1·11, 95% CI 0·96-1·27; p=0·17). The prevalence of anxiety was 17·9% (95% CI 12·8-23·6) in 48u2008964 cancer survivors and 13·9% (9·8-18·5) in 226u2008467 healthy controls (RR 1·27, 95% CI 1·08-1·50; p=0·0039). Neither the prevalence of depression (26·7% vs 26·3%; RR 1·01, 95% CI 0·86-1·20; p=0·88) nor the prevalence of anxiety (28·0% vs 40·1%; RR 0·71, 95% CI 0·44-1·14; p=0·16) differed significantly between cancer patients and their spouses.nnnINTERPRETATIONnOur findings suggest that anxiety, rather than depression, is most likely to be a problem in long-term cancer survivors and spouses compared with healthy controls. Efforts should be made to improve recognition and treatment of anxiety in long-term cancer survivors and their spouses.nnnFUNDINGnNone.

A genome wide association study (GWAS) providing evidence of an association between common genetic variants and late radiotherapy toxicity

BACKGROUND AND PURPOSEnThis study was designed to identify common single nucleotide polymorphisms (SNPs) associated with toxicity 2years after radiotherapy.nnnMATERIALS AND METHODSnA genome wide association study was performed in 1850 patients from the RAPPER study: 1217 received adjuvant breast radiotherapy and 633 had radical prostate radiotherapy. Genotype associations with both overall and individual endpoints of toxicity were tested via univariable and multivariable regression. Replication of potentially associated SNPs was carried out in three independent patient cohorts who had radiotherapy for prostate (516 RADIOGEN and 862 Gene-PARE) or breast (355 LeND) cancer.nnnRESULTSnQuantile-quantile plots show more associations at the P<5×10(-7) level than expected by chance (164 vs. 9 for the prostate cases and 29 vs. 4 for breast cases), providing evidence that common genetic variants are associated with risk of toxicity. Strongest associations were for individual endpoints rather than an overall measure of toxicity in all patients. However, in general, significant associations were not validated at a nominal 0.05 level in the replication cohorts.nnnCONCLUSIONSnThis largest GWAS to date provides evidence of true association between common genetic variants and toxicity. Associations with toxicity appeared to be tumour site-specific. Future GWAS require higher statistical power, in particular in the validation stage, to test clinically relevant effect sizes of SNP associations with individual endpoints, but the required sample sizes are achievable.

Retinoic acid and retinoid receptors: potential chemopreventive and therapeutic role in cervical cancer

Retinoids are natural and synthetic derivatives of vitamin A, which can be obtained from animal products (milk, liver, beef, fish oils, and eggs) and vegetables (carrots, mangos, sweet potatoes, and spinach). Retinoids regulate various important cellular functions in the body through specific nuclear retinoic-acid receptors and retinoid-X receptors, which are encoded by separate genes. Retinoic-acid receptors specifically bind tretinoin and alitretinoin, whereas retinoid-X receptors bind only alitretinoin. Retinoids have long been established as crucial for several essential life processes-healthy growth, vision, maintenance of tissues, reproduction, metabolism, tissue differentiation (normal, premalignant cells, and malignant cells), haemopoiesis, bone development, spermatogenesis, embryogenesis, and overall survival. Therefore, deficiency of vitamin A can lead to various unwanted biological effects. Several experimental and epidemiological studies have shown the antiproliferative activity of retinoids and their potential use in cancer treatment and chemoprevention. Emerging clinical trials have shown the chemotherapeutic and chemopreventive potential of retinoids in cancerous and precancerous conditions of the uterine cervix. In this review, we explore the potential chemopreventive and therapeutic roles of retinoids in preinvasive and invasive cervical neoplasia.

Which symptoms are indicative of depression in epilepsy settings? An analysis of the diagnostic significance of somatic and non-somatic symptoms

BACKGROUNDnThere have been few studies that have attempted to examine the phenomenology of comorbid depression, in particular the diagnostic value of individual somatic and non-somatic symptoms when attempting to diagnose depression following cancer.nnnMETHODSnWe approached 279 patients up to three times within 9 months of first presentation with a diagnosis of cancer, and collected data following a total of 558 contacts. 176 contacts (31%) were in a palliative stage. Symptoms were elicited by self-report PHQ9 and HADS-D scales. The prevalence of major depression was 12.7% but 29.6% had major or minor depression (any depressive disorder) according to modified DSMIV criteria.nnnRESULTSnAll symptoms of depression were significant more common in depressed versus non-depressed cancer patients regardless of stage. Against broadly defined any depressive disorder (ADD) the most accurate diagnostic symptoms were all somatic (namely trouble falling or staying asleep or sleeping too much; feeling tired or having little energy; poor appetite or overeating; trouble concentrating on things such as reading). Indeed the optimal symptom insomnia had good case-finding properties and screening properties used alone. A two step combination of three questions give a sensitivity of 100% and specificity of 91.6% against ADD. Against major depressive disorder (MDD) both somatic and non-somatic symptoms were valuable (including but not limited to the PHQ2 stem questions). Only low energy was poorly discriminating which may suggest that the standard ICD10 criteria may not be optimal. When considering depression as defined by the HADS-D (≥ 11), then the three most influential symptoms were psychological closely followed by somatic symptoms. When looking for MDD and HADS-D depression, no single symptom was a good proxy for depression highlighting a possible shortcoming if clinicians attempt to rely on one single question. In a subset of palliative patients feeling bad about yourself and moving or speaking slowly were less influential and outperformed by poor appetite/overeating and feeling tired or having little energy.nnnCONCLUSIONnThis research suggests that most somatic symptoms remain influential when diagnosing depression in the context of cancer and hence should not be omitted indiscriminately, even in palliative stages. The optimal symptoms for diagnosing depression will depend on whether a narrow concept of depression or a broad concept of depression is considered clinically important.

How feasible is implementation of distress screening by cancer clinicians in routine clinical care

There is considerable uncertainty regarding the acceptability of routine distress screening.

Radiation exposure and health effects - is it time to reassess the real consequences?

Our acceptance of exposure to radiation is somewhat schizophrenic. We accept that the use of high doses of radiation is still one of the most valuable weapons in our fight against cancer, and believe that bathing in radioactive spas is beneficial. On the other hand, as a species, we are fearful of exposure to man-made radiation as a result of accidents related to power generation, even though we understand that the doses are orders of magnitude lower than those we use everyday in medicine. The 70th anniversary of the detonation of the atomic bombs in Hiroshima and Nagasaki was marked in 2015. The 30th anniversary of the Chernobyl nuclear power plant accident will be marked in April 2016. March 2016 also sees the fifth anniversary of the accident at the Fukushima nuclear power plant. Perhaps now is an opportune time to assess whether we are right to be fearful of the effects of low doses of radiation, or whether actions taken because of our fear of radiation actually cause a greater detriment to health than the direct effect of radiation exposure.

Changes in the treatment of endometrial cancer

Please cite this paper as: Faust G, Davies Q, Symonds P. Changes in the treatment of endometrial cancer. BJOG 2010;117:1043–1046.

Chemotherapy and Radiotherapy in Gynaecological Cancer

Chemotherapy kills cancer largely by damaging tumour DNA and preventing replication. It can be used for cure, symptom control, to reduce risks of recurrence or to make other cancer treatments such as radiotherapy more effective. Radiotherapy is the use of ionising radiation to kill cancers. It is usually given in multiple treatments (fractions) to minimise damage to normal tissue. Both modalities are widely used in the treatment of gynaecological cancers. This chapter deals with litigation related to their usage.

Life After Urological Cancer – Psychological Issues

About half of patients treated for urological cancer will experience some degree of psychological distress and about a quarter have some degree of depression at some time in their illness. Patients with prostate cancer have lower levels of anxiety and depression compared to some other cancers. Psychological symptoms may be overshadowed by physical symptoms. However, useful clinical screening tests include the simple question “are you feeling down, depressed or hopeless?” and questions about sleep disturbance may identify depressed patients. The diagnosis of anxiety and depression may be helped by screening tools such as the Hospital Anxiety and Depression Scale (HADS) but we have found simple analogue scales (the Emotion Thermometers) much less laborious to use and equally accurate. Fatigue is one of the most common symptoms amongst cancer patients and can be worsened by radiotherapy and the use of androgen deprivation therapy (ADT). Fatigue is associated with depression in about half of patients. Graded aerobic exercise programmes should be considered for patients suffering from fatigue rather than the classical advice of rest, which could be detrimental. Minor degrees of cognitive dysfunction particularly reduction in immediate and working memory are common in men treated with ADT and occasionally can be severe. Recognition and treatment of distress, anxiety and depression can markedly improve the quality of life in patients treated for urological cancer.

A smear on audit

The smear history of 403 women who developed invasive cervical cancer in Leicester between January 1993 and September 2000 were reviewed in a retrospective audit. The aim of the audit was ‘to ascertain whether diagnosis could potentially have been made sooner and to identify improvements that could have been made within the laboratory aspect of the screening service’. Three hundred and twenty-four (80%) of these women had a cervical smear before diagnosis and their test results were reexamined. In 84 women, a false negative report had been issued; in 38 women, the cytological abnormality had been undergraded. The consequences of these misinterpretations were serious. Twenty of these 122 women died, diagnostic delay being an important factor in 14 deaths. The same diagnostic delay led to 64 women having more radical treatment than would have been otherwise required. During this time, the Leicester laboratory examined approximately 80,000 cervical smears annually. The managers of the service were informed of these results before they were submitted to a scientific journal. This led to an internal debate about how to handle the information. Eventually, advice was sought from the Department of Health. A decision was made at ministerial level to release these data at a press conference and to tell the women or their bereaved relatives the results of individual reviews of previous cytological examinations. In our view, this decision has profound consequences for clinical audit. It breached the principle of confidentiality of audit; it exposed the Trust and the NHS to possible litigation, and could adversely affect confidence in the cervical screening programme. Moreover, this decision has implications for many other branches of medicine.