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Computer-aided detection for reading mammograms
Gilbert FJ, Astley SM, Gillan MCG et al. Single reading with computer-aided detection for screening mammography. N Engl J Med 2008; 359: 1675-84

For breast cancer screening, mammograms using single reading with computer-aided detection (CAD) offer an alternative to double reading, according to this study. The sensitivity of screening mammography for detecting small breast cancer has been shown to be higher when a mammogram is read by two readers as opposed to one, with studies suggesting that double reading increases the rate of cancer detection by 4-14 per cent and by 10 per cent according to a meta-analysis. Double reading is now standard practice in at least 12 European countries.

CAD systems use computer algorithms to analyse digital mammographic images, and identify and mark potentially suspicious regions that attract the radiologist's attention to features that might otherwise be overlooked. In the US, where single reading is standard practice, CAD systems are used in 25-30 per cent of all mammogram readings.

This study set out to determine whether the performance of a single reader using a CAD system would match that achieved by two separate readers. Between September 2006 and August 2007, 31,057 women undergoing routine screening by film mammography at centres in England were randomly assigned to one of three reading regimens.

In the study, group A (with a planned number of 1,000 subjects) was assigned to receive double reading only, group B (with a planned number of 1,000 subjects) was assigned to receive single reading with CAD and group C (with a planned number of 28,000 subjects) was assigned to receive a single reading with CAD and a double reading.

Overall results show that for group C, 227 cancers were detected among 28,204 subjects. When double reading was considered separately, the proportion of cancers detected was 199 out of 227 (87.7 per cent) and when single reading with CAD was considered separately, the proportion of cancers detected was 198 out of 227 (87.2 per cent), providing a p value of 0.89.

The results produced cancer detection rates of 7.02 per 1,000 for the single reader using CAD and 7.06 per 1,000 for two readers. Additionally, the overall recall rates were 3.9 per cent for the single reading group with CAD and 3.4 per cent for the double reading group (p <0.001).

For single reading with CAD, estimated sensitivity was 87.2 per cent, specificity, 96.9 per cent, and positive predictive value, 18.0 per cent. For double reading, the figures were 87.7 per cent, 97.4 per cent and 21.1 per cent, respectively.

The authors concluded that single reading with CAD offers an alternative to double reading. They also recommended that the performance of CAD in full-field digital mammography and its performance in film mammography, used in the current study, should be investigated.

The risk of suicidal thoughts in patients who have cancer
Misono S, Weiss N, Fann J et al. J Clin Oncol 2008; 26(29): 4731-8
Walker J, Waters R, Murray G et al. J Clin Oncol 2008; 26(29): 4725-30.
Quill T. J Clin Oncol 2008; 26(29): 4705-7

Two separate studies provide valuable insights into the risk of suicide among patients with cancer. One reveals that cancer patients are almost twice as likely to commit suicide as the general US population, while the other, from the UK, found that a substantial number of cancer patients report thoughts that they would be 'better off dead', or of 'hurting themselves'.

Improved survival after treatment has heightened the need for developing better understanding of questions surrounding cancer survivorship and quality of life. Most previous studies on suicide and depression have focused on terminally ill patients, with little work undertaken in broader cancer populations, including patients likely to be long-term survivors.

In the first study, researchers compared the incidence of suicide among cancer patients with that of the general population. Comparisons were based on mortality data collected by the US National Center for Health Statistics. This is the first time such comparisons have been made in the US.

Additionally, the investigators set out to identify disease characteristics, such as the anatomic site of cancers, associated with particularly high suicide rates. A total of 5,838 suicides were identified among 3,594,750 persons with cancer observed for 18,604,308 person-years, giving an age-, sex- and race-adjusted suicide rate of 31.4 per 100,000 person-years. The corresponding rate for the general US population was found to be 16.7 per 100,000 person-years. Statistical analysis produced a standardised mortality ratio of 1.88, meaning cancer patients were 1.88 times as likely to commit suicide.

Higher suicide rates among patients with cancer were associated with male sex, white race and being unmarried. Rates were also higher among patients with advanced disease at diagnosis, but not among those with multiple primary tumours. They were highest among patients with cancers of the lung and bronchus (81.7 per 100,000 person-years), followed by stomach (71.7 per 100,000 person-years) and cancers of the oral cavity and pharynx (53.1 per 100,000 person-years).

The authors speculated that patients with lung cancer may struggle with their grave prognoses, while head and neck cancers can have a particularly devastating effect on quality of life 'through impact on appearance and essential functions, such as speech, swallowing and breathing'.

They also suggested that the psychological experience of cancer survivors deserved further attention, particularly because appropriate use of psychosocial interventions in patients with cancer can improve their quality of life.

Limitations of the study included causes of death being subject to misclassification, inability to evaluate the potentially confounding role of comorbid conditions and inability to identify patients with cancer who committed suicide from the general population data.

In the second study, UK researchers surveyed 2,924 consecutive patients attending a cancer outpatient clinic between June 2003 and December 2004. The investigators used the nine-item Patient Health Questionnaire (PHQ-9), a widely used self-report screening tool, which included the critical question (item nine) asking whether patients had entertained thoughts of being 'better off dead or of hurting themselves in some way' in the previous two weeks.

Results were available on 2,924 patients, with 7.8 per cent (229 out of 2,924) responding positively to item nine. Of these, 5.4 per cent (159 out of 2,924) reported experiencing such thoughts on several days over the two-week period, 1.6 per cent (46 out of 2,924) on more than half the days and 0.8 per cent (24 out of 2,924) nearly every day. When demographic and clinical variables were considered, clinically significant emotional distress and substantial pain (and to a lesser extent, older age) were the only variables found to be associated with a positive response.

Limitations of the study include the fact that it used a self-completed screening measure, rather than an interview, so the investigators had to rely on patients' interpretation of the questions. Furthermore, the study did not include all of the factors that might be associated with thoughts of being 'better off dead or of hurting yourself', such as the patients' general health and social support.

In an accompanying editorial, Dr Timothy Quill, director of the palliative care program, University of Rochester Medical Center, New York, wrote: 'Qualitative studies will be needed to deepen our understanding of the range of thoughts, feelings, hopes and fears present in many seriously ill patients, so we can better distinguish clinical depression and anxiety that might be amenable to medical treatment from the range of normal sadness and fear that can be acknowledged and explored, but not necessarily treated.'

Systematic screening, he added, was essential: 'It is important to ask about suicidal thoughts and intent regularly, especially at times of transition when disease is worsening, symptoms are increasing or the patient is entering a more serious phase of illness. Creating an environment where these issues can be openly explored without being judged is critical.'

Risk of breast cancer after tangential fields radiotherapy
Hooning MJ, Aleman BMP, Hauptmann M et al. Roles of radiotherapy and chemotherapy in the development of contralateral breast cancer. J Clin Oncol 2008; 26: 5561-68 

Women with breast cancer treated with radiotherapy using tangential fields - where radiation is directed at an angle to the breast - after lumpectomy show increased risk of cancer in the other breast, with an even higher risk in younger women and in those with family members who have had breast cancer.

Women who have had breast cancer have a three to four times higher risk of developing a new primary cancer in their other breast (contralateral breast cancer), compared with the risk of a first primary breast cancer in other women. This increased risk could be due to a common cause for the tumours in both breasts, such as a genetic tendency or hormonal risk factors.

Few studies have looked at whether modern radiotherapy and chemotherapy affect this risk, so a large study was carried out to assess the long-term risk of contralateral breast cancer in young women, focusing on the effects of radiation dose, chemotherapy and their family history of breast cancer.

The study included 7,221 predominantly young women treated for breast cancer at two centres in the Netherlands between 1970 and 1986. The researchers searched the patients' records for information on the treatment for their primary cancers (surgery, radiotherapy, chemotherapy and hormonal), whether they suffered recurrent cancer and their family history of breast cancer.

Results showed that radiotherapy did not significantly increase the risk of contralateral breast cancer overall. However, the risk associated with radiotherapy was higher in younger women. Those younger than 35 years at first treatment had nearly twice the risk of breast cancer associated with radiotherapy in the other breast (HR 1.78; 95% CI, 0.85-3.72) compared to women over 45 years (HR 1.09; 95% CI, 0.82-1.45).

The risk of contralateral breast cancer also depended on the type of radiotherapy, which was determined by the location and stage of the primary cancer. Women treated before the age of 45 years with radiotherapy after lumpectomy showed a 1.5-fold increased risk of cancer in their other breast compared with those who had radiotherapy after mastectomy.

The researchers suggested that the difference might have occurred because post-mastectomy radiotherapy using direct electron fields led to a significantly lower radiation exposure to the contralateral breast than post-lumpectomy radiotherapy using tangential fields.

Treatment with adjuvant chemotherapy (cyclophosphamide, methotrexate and fluorouracil) was associated with a non-significantly decreased risk of contralateral breast cancer in the first five years of follow-up, but did not reduce the risk in subsequent years.

Summaries provided by the European School of Oncology's Cancer Media Service

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