- Email: [email protected]
MRI breast screening
Correspondence
*Timothy D Girard, John P Kress, Barry D Fuchs, Gordon R Bernard, E Wesley Ely [email protected] Vanderbilt University School of Medicine, Nashville, TN 37232, USA (TDG, GRB, EWE); University of Chicago, Chicago, IL, USA (JPK); and University of Pennsylvania Schoo l of Medicine, Philadelphia, PA, USA (BDF) 1
2
3
4
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Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med 2002; 166: 1338–44. Weinert CR, Calvin AD. Epidemiology of sedation and sedation adequacy for mechanically ventilated patients in a medical and surgical intensive care unit. Crit Care Med 2007; 35: 393–401. Payen JF, Chanques G, Mantz J, et al. Current practices in sedation and analgesia for mechanically ventilated critically ill patients: a prospective multicenter patient-based study. Anesthesiology 2007; 106: 687–95. Esteban A, Frutos F, Tobin MJ, et al. A comparison of four methods of weaning patients from mechanical ventilation. N Engl J Med 1995; 332: 345–50. Kress JP, Pohlman AS, O’Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000; 342: 1471–77.
MRI breast screening We are disturbed by the misrepresentation of some facts by Christiane Kuhl and colleagues (Dec 8, p 1903)1 in their reply to our letters.2,3 They play down the cost of MRI by comparing it to digital and not conventional mammography, which is still the standard of care around the world. Similarly, they do not mention that, for every one life prolonged by mammographic screening, 10 women are diagnosed with breast cancer who would not otherwise have received this diagnosis in their lifetime.4 Kuhl and colleagues state: “This is the conditional benefit of screening—a concept women seem www.thelancet.com Vol 371 April 26, 2006
to understand rather better than many epidemiologists”, without acknowledging the fact that most women are still not aware of the intricate details needed to make an informed decision. Kuhl and colleagues state that ductal carcinoma in situ progresses to invasive cancer on most occasions; yet evidence from autopsy studies5 indicates that most does not progress to the invasive stage, and can even regress. Kuhl and colleagues also state “we should not prematurely reject a new diagnostic tool for an added (negative) effect on a small problem, as long as it has a substantial (positive) effect on a big problem”. But a good diagnostic tool does not necessarily equate to an acceptable screening tool. The former is applied to patients and the latter to asymptomatic women: the intentions, benefits, costs (both economic and psychological), and potential for harm are entirely different. We do not necessarily oppose further research, but would favour either a well organised open public debate informed by facts or a citizens’ deliberation. On the basis of current evidence, the likelihood that MRI screening will result in improvements that justify the costs and agony of overdiagnoses is questionable. Let society decide whether it wants to explore this minuscule chance.
Christiane Kuhl and co-workers1 provide interesting insights into the diagnosis of ductal carcinoma in situ (DCIS) and its natural evolution in a very large single-centre study. Most importantly this study shows that MRI has increased sensitivity in highgrade (98%) compared with low-grade and intermediate-grade DCIS (85%, p=0·002; value obtained retrospectively by us based on the data). Kuhl and colleagues avoided many of the biases in previous diagnostic trials on the topic (such as inclusion of typical DCIS mammographies),2 and analysed both MRI and mammography independently and blinded to the results of the other modality and the reference test. However, positive mammography tests triggered 56% of all MRIs and the decision to do the reference test (biopsy procedures) also in this study depended on a positive result in at least one of the two index tests (partial verification bias)3 since other approaches would be unethical. One can, however, adjust for this bias and recalculate sensitivities using the formula:
We declare that we have no conflict of interest.
In this formula the odds ratio describes whether the errors of the diagnostic procedures are based on the same or different properties of the tumours. With this approach, and with the numbers in Kuhl and colleagues’ figure 1, we recalculated the sensitivities. The table shows two different scenarios: (1) false negative results appear independently and (2) a false negative result is about twice as probable in MRI if it was false negative in mammography and vice versa (as quantified by the odds ratio). We agree with Kuhl and colleagues that the comparison of MRI and mammography is also valid under partial verification. However, the naively determined sensitivities are somewhat
*Mangesh A Thorat, Hazel Thornton [email protected] Department of Pathology and Laboratory Medicine, IU School of Medicine, 635 Barnhill Drive, MS-A128, Indianapolis, IN 46202, USA (MT); and Department of Health Sciences, University of Leicester, Leicester, UK (HT) 1
2 3 4
5
Kuhl C, Schrading S, Wardelmann E, Kuhn W, Schild H. Should we undertake an MRI breast screening trial? Lancet 2007; 370: 1903–04. Thorat MA. Should we undertake an MRI breast screening trial? Lancet 2007; 370: 1902. Thornton H. Should we undertake an MRI breast screening trial? Lancet 2007; 370: 1903. Gøtzsche PC, Nielsen M. Screening for breast cancer with mammography. Cochrane Database Syst Rev 2006; 4: CD001877. Nielsen M, Thomsen JL, Primdahl S, Dyreborg U, Andersen JA. Breast cancer and atypia among young and middle-aged women: a study of 110 medicolegal autopsies. Br J Cancer 1987; 56: 814–19.
n (both false negative)= odds ratio × n (only MRI positive) × n (only mammography positive) n (both positive)
Science Photo Library
was studied. We agree with Siegel that excess sedation should be avoided, but light sedation and the ABC protocol are not mutually exclusive. On the basis of our results, we recommend the “wake up and breathe” protocol for the management of mechanically ventilated intensive-care patients who are heavily or lightly sedated.
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*Timothy D Girard, John P Kress, Barry D Fuchs, Gordon R Bernard, E Wesley Ely [email protected] Vanderbilt University School of Medicine, Nashville, TN 37232, USA (TDG, GRB, EWE); University of Chicago, Chicago, IL, USA (JPK); and University of Pennsylvania Schoo l of Medicine, Philadelphia, PA, USA (BDF) 1
2
3
4
5
Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med 2002; 166: 1338–44. Weinert CR, Calvin AD. Epidemiology of sedation and sedation adequacy for mechanically ventilated patients in a medical and surgical intensive care unit. Crit Care Med 2007; 35: 393–401. Payen JF, Chanques G, Mantz J, et al. Current practices in sedation and analgesia for mechanically ventilated critically ill patients: a prospective multicenter patient-based study. Anesthesiology 2007; 106: 687–95. Esteban A, Frutos F, Tobin MJ, et al. A comparison of four methods of weaning patients from mechanical ventilation. N Engl J Med 1995; 332: 345–50. Kress JP, Pohlman AS, O’Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000; 342: 1471–77.
MRI breast screening We are disturbed by the misrepresentation of some facts by Christiane Kuhl and colleagues (Dec 8, p 1903)1 in their reply to our letters.2,3 They play down the cost of MRI by comparing it to digital and not conventional mammography, which is still the standard of care around the world. Similarly, they do not mention that, for every one life prolonged by mammographic screening, 10 women are diagnosed with breast cancer who would not otherwise have received this diagnosis in their lifetime.4 Kuhl and colleagues state: “This is the conditional benefit of screening—a concept women seem www.thelancet.com Vol 371 April 26, 2006
to understand rather better than many epidemiologists”, without acknowledging the fact that most women are still not aware of the intricate details needed to make an informed decision. Kuhl and colleagues state that ductal carcinoma in situ progresses to invasive cancer on most occasions; yet evidence from autopsy studies5 indicates that most does not progress to the invasive stage, and can even regress. Kuhl and colleagues also state “we should not prematurely reject a new diagnostic tool for an added (negative) effect on a small problem, as long as it has a substantial (positive) effect on a big problem”. But a good diagnostic tool does not necessarily equate to an acceptable screening tool. The former is applied to patients and the latter to asymptomatic women: the intentions, benefits, costs (both economic and psychological), and potential for harm are entirely different. We do not necessarily oppose further research, but would favour either a well organised open public debate informed by facts or a citizens’ deliberation. On the basis of current evidence, the likelihood that MRI screening will result in improvements that justify the costs and agony of overdiagnoses is questionable. Let society decide whether it wants to explore this minuscule chance.
Christiane Kuhl and co-workers1 provide interesting insights into the diagnosis of ductal carcinoma in situ (DCIS) and its natural evolution in a very large single-centre study. Most importantly this study shows that MRI has increased sensitivity in highgrade (98%) compared with low-grade and intermediate-grade DCIS (85%, p=0·002; value obtained retrospectively by us based on the data). Kuhl and colleagues avoided many of the biases in previous diagnostic trials on the topic (such as inclusion of typical DCIS mammographies),2 and analysed both MRI and mammography independently and blinded to the results of the other modality and the reference test. However, positive mammography tests triggered 56% of all MRIs and the decision to do the reference test (biopsy procedures) also in this study depended on a positive result in at least one of the two index tests (partial verification bias)3 since other approaches would be unethical. One can, however, adjust for this bias and recalculate sensitivities using the formula:
We declare that we have no conflict of interest.
In this formula the odds ratio describes whether the errors of the diagnostic procedures are based on the same or different properties of the tumours. With this approach, and with the numbers in Kuhl and colleagues’ figure 1, we recalculated the sensitivities. The table shows two different scenarios: (1) false negative results appear independently and (2) a false negative result is about twice as probable in MRI if it was false negative in mammography and vice versa (as quantified by the odds ratio). We agree with Kuhl and colleagues that the comparison of MRI and mammography is also valid under partial verification. However, the naively determined sensitivities are somewhat
*Mangesh A Thorat, Hazel Thornton [email protected] Department of Pathology and Laboratory Medicine, IU School of Medicine, 635 Barnhill Drive, MS-A128, Indianapolis, IN 46202, USA (MT); and Department of Health Sciences, University of Leicester, Leicester, UK (HT) 1
2 3 4
5
Kuhl C, Schrading S, Wardelmann E, Kuhn W, Schild H. Should we undertake an MRI breast screening trial? Lancet 2007; 370: 1903–04. Thorat MA. Should we undertake an MRI breast screening trial? Lancet 2007; 370: 1902. Thornton H. Should we undertake an MRI breast screening trial? Lancet 2007; 370: 1903. Gøtzsche PC, Nielsen M. Screening for breast cancer with mammography. Cochrane Database Syst Rev 2006; 4: CD001877. Nielsen M, Thomsen JL, Primdahl S, Dyreborg U, Andersen JA. Breast cancer and atypia among young and middle-aged women: a study of 110 medicolegal autopsies. Br J Cancer 1987; 56: 814–19.
n (both false negative)= odds ratio × n (only MRI positive) × n (only mammography positive) n (both positive)
Science Photo Library
was studied. We agree with Siegel that excess sedation should be avoided, but light sedation and the ABC protocol are not mutually exclusive. On the basis of our results, we recommend the “wake up and breathe” protocol for the management of mechanically ventilated intensive-care patients who are heavily or lightly sedated.
1415