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In Response to Glatstein (Int J Radiat Oncol Biol Phys 2007;68:322)
Int. J. Radiation Oncology Biol. Phys., Vol. 70, No. 3, pp. 961–965, 2008 Copyright Ó 2008 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/08/$–see front matter
LETTERS TO THE EDITOR IN RESPONSE TO GLATSTEIN (INT J RADIAT ONCOL BIOL PHYS 2007;68:322)
1. Fatunase T, Wang Z, Yoo S, et al. Assessment of the residual error in soft tissue setup in patients undergoing partial breast irradiation: Results of a prospective study using cone-beam computed tomography. Int J Radiat Oncol Biol Phys 2007, Sept 22 [Epub ahead of print]. 2. White EA, Cho J, Vallis KA, et al. Cone beam computed tomography guidance for setup of patients receiving accelerated partial breast irradiation. Int J Radiat Oncol Biol Phys 2007;68:547–554. 3. van Herk M. Errors and margins in radiotherapy. Semin Radiat Oncol 2005;14:52–64.
To the Editor: A recent editorial (1) crisply summarized the problems in celebrating small advantages in huge studies. Another issue might be mentioned, as the editorial referred to absolute survival, the time-tested way of measuring therapeutic efficacy. Absolute survival has been frequently abandoned, both in print and in practice, for percentage increase in survival—or worse, simply in response rates. In other words, a breast cancer patient with a 90% chance of living with no treatment and a 93.3% chance of living with treatment will be told she has a 30% advantage in taking treatment. The more sober among us might say she has a 3.3% increase in survival with treatment. This falls under the rubric of Lies, Damn lies, and Statistics.
SUBJECTIVE RATINGS VS. OBJECTIVE MEASUREMENT OF COGNITIVE FUNCTION: IN REGARD TO VAN BEEK ET AL. (INT J RADIAT ONCOL BIOL PHYS 2007;68:986–991)
THOMAS EDWARD GOFFMAN, M.D., F.A.C.P. Cancer Intelligence and Research PC Virginia Beach, VA
To the Editor: We read with great interest the manuscript of van Beek et al. (1), in which the authors report on the impact of radiotherapy on long-term health-related quality of life (HRQOL) and cognitive problems among patients treated for nonfunctioning pituitary adenoma. After treatment, HRQOL, depression, fatigue, and cognitive functioning of irradiated and unirradiated patients was assessed using self-report questionnaires. Patients with or without radiotherapy attained comparable HRQOL scores in most domains and radiotherapy was even significantly associated with improved HRQOL in a multivariate model. No differences in cognitive function scores were observed. Although we think that studies into the cognitive effects of treatment of these patients should be strongly encouraged, we would at the same time like to caution against the use of self-report questionnaires as a means to measure cognitive functioning. Numerous studies that focus on perceptions of cognitive functioning have consistently found these self-reports to be unrelated to objective performance in distinct patient groups, including those with cancer (2), coronary artery bypass surgery (3, 4), multiple sclerosis (5, 6), temporal lobe epilepsy surgery (7), and HIV (8). In cancer patients, and potentially also in those with pituitary adenomas, cognitive complaints might more likely reflect feelings of anxiety, depression, and fatigue than a loss of cognitive abilities (2). Considering the elevated levels of depression and fatigue in the study of van Beek and colleagues, this is most likely also the case in patients with nonfunctioning pituitary adenoma. We suggest these findings strongly argue against relying on patient reports to assess cognitive function. Objective testing remains the method of choice for assessing higher cognitive functions.
doi:10.1016/j.ijrobp.2007.11.017 1. Glatstein E. Restrictions of a statistical mind: Clinical relevance versus P values or when less is more. Int J Radiat Oncol Biol Phys 2007;68:322.
ON THE USE OF THE TERM ‘‘SYSTEMATIC ERROR’’: IN REGARD TO FATUNASE ET AL. (INT J RADIAT ONCOL BIOL PHYS; IN PRESS) To the Editor: In a recent article on cone-beam computed tomographic assessment of setup error in accelerated partial breast patients (1), Fatunase et al. compare their results to a similar, previous study by White et al. (2). They assert that there is a difference between the two studies, in that White et al. found ‘‘systematic errors’’ in skin-mark–based setups, whereas Fatunase et al. ‘‘did not observe systematic errors (our mean error was \1 mm).’’ There is more than one current usage for the term ‘‘systematic error.’’ One usage (patient-specific systematic error) refers to a setup error that persists in magnitude and direction throughout the treatment course of an individual patient. The other usage (group or process systematic error) refers to a setup error that is common to an entire patient population. The problem is that neither study qualifies or defines their use of the term ‘‘systematic error,’’ and it appears that White et al. use the term in the former sense whereas Fatunase et al. use it in the latter. In actuality, the results of the two studies appear consistent. In their paper White et al. state, ‘‘The mean of all means for both setup methods was \1 mm.’’ It is this result that Fatunase et al. should have compared with their own finding of no [group or process] systematic error. On the flip side, White et al.’s ‘‘systematic error’’ appears to refer to the standard deviation of individual patient mean setup errors (S), assuming that they are following van Herk (3), whom they cite in their paper. If one computes this same quantity from the data presented by Fatunase et al., one obtains 1.9, 2.5, and 2.0 mm in the right–left, anterior–posterior, and superior–inferior directions, respectively. This compares well with the White et al. published values of 2.7, 1.7, and 2.4 mm. Authors and reviewers are advised to be wary of indiscriminate use of the term ‘‘systematic error’’ (as well as ‘‘random error’’). They may refer to different quantities, depending on whether one is speaking within a global or patient-specific context. To avoid ambiguity and confusion, such terms should always be defined mathematically within any given study.
MARTIN KLEIN, PH.D. Department of Medical Psychology JAAP C. REIJNEVELD, M.D., PH.D. JAN J. HEIMANS, M.D., PH.D. Department of Neurology VU University Medical Center Amsterdam, The Netherlands doi:10.1016/j.ijrobp.2007.09.031 1. van Beek AP, van den Bergh AC, van den Berg LM, et al. Radiotherapy is not associated with reduced quality of life and cognitive function in patients treated for nonfunctioning pituitary adenoma. Int J Radiat Oncol Biol Phys 2007;68:986–991. 2. Cull A, Hay C, Love SB, et al. What do cancer patients mean when they complain of concentration and memory problems? Br J Cancer 1996;74: 1674–1679. 3. Newman S, Klinger L, Venn G, et al. Subjective reports of cognition in relation to assessed cognitive performance following coronary artery bypass surgery. J Psychosom Res 1989;33:227–233. 4. Khatri P, Babyak M, Clancy C, et al. Perception of cognitive function in older adults. Health Psychol 1999;18:301–306.
LEONARD KIM, M.S., A.MUS.D. Department of Radiation Oncology William Beaumont Hospital Royal Oak, MI doi:10.1016/j.ijrobp.2007.10.035 961
LETTERS TO THE EDITOR IN RESPONSE TO GLATSTEIN (INT J RADIAT ONCOL BIOL PHYS 2007;68:322)
1. Fatunase T, Wang Z, Yoo S, et al. Assessment of the residual error in soft tissue setup in patients undergoing partial breast irradiation: Results of a prospective study using cone-beam computed tomography. Int J Radiat Oncol Biol Phys 2007, Sept 22 [Epub ahead of print]. 2. White EA, Cho J, Vallis KA, et al. Cone beam computed tomography guidance for setup of patients receiving accelerated partial breast irradiation. Int J Radiat Oncol Biol Phys 2007;68:547–554. 3. van Herk M. Errors and margins in radiotherapy. Semin Radiat Oncol 2005;14:52–64.
To the Editor: A recent editorial (1) crisply summarized the problems in celebrating small advantages in huge studies. Another issue might be mentioned, as the editorial referred to absolute survival, the time-tested way of measuring therapeutic efficacy. Absolute survival has been frequently abandoned, both in print and in practice, for percentage increase in survival—or worse, simply in response rates. In other words, a breast cancer patient with a 90% chance of living with no treatment and a 93.3% chance of living with treatment will be told she has a 30% advantage in taking treatment. The more sober among us might say she has a 3.3% increase in survival with treatment. This falls under the rubric of Lies, Damn lies, and Statistics.
SUBJECTIVE RATINGS VS. OBJECTIVE MEASUREMENT OF COGNITIVE FUNCTION: IN REGARD TO VAN BEEK ET AL. (INT J RADIAT ONCOL BIOL PHYS 2007;68:986–991)
THOMAS EDWARD GOFFMAN, M.D., F.A.C.P. Cancer Intelligence and Research PC Virginia Beach, VA
To the Editor: We read with great interest the manuscript of van Beek et al. (1), in which the authors report on the impact of radiotherapy on long-term health-related quality of life (HRQOL) and cognitive problems among patients treated for nonfunctioning pituitary adenoma. After treatment, HRQOL, depression, fatigue, and cognitive functioning of irradiated and unirradiated patients was assessed using self-report questionnaires. Patients with or without radiotherapy attained comparable HRQOL scores in most domains and radiotherapy was even significantly associated with improved HRQOL in a multivariate model. No differences in cognitive function scores were observed. Although we think that studies into the cognitive effects of treatment of these patients should be strongly encouraged, we would at the same time like to caution against the use of self-report questionnaires as a means to measure cognitive functioning. Numerous studies that focus on perceptions of cognitive functioning have consistently found these self-reports to be unrelated to objective performance in distinct patient groups, including those with cancer (2), coronary artery bypass surgery (3, 4), multiple sclerosis (5, 6), temporal lobe epilepsy surgery (7), and HIV (8). In cancer patients, and potentially also in those with pituitary adenomas, cognitive complaints might more likely reflect feelings of anxiety, depression, and fatigue than a loss of cognitive abilities (2). Considering the elevated levels of depression and fatigue in the study of van Beek and colleagues, this is most likely also the case in patients with nonfunctioning pituitary adenoma. We suggest these findings strongly argue against relying on patient reports to assess cognitive function. Objective testing remains the method of choice for assessing higher cognitive functions.
doi:10.1016/j.ijrobp.2007.11.017 1. Glatstein E. Restrictions of a statistical mind: Clinical relevance versus P values or when less is more. Int J Radiat Oncol Biol Phys 2007;68:322.
ON THE USE OF THE TERM ‘‘SYSTEMATIC ERROR’’: IN REGARD TO FATUNASE ET AL. (INT J RADIAT ONCOL BIOL PHYS; IN PRESS) To the Editor: In a recent article on cone-beam computed tomographic assessment of setup error in accelerated partial breast patients (1), Fatunase et al. compare their results to a similar, previous study by White et al. (2). They assert that there is a difference between the two studies, in that White et al. found ‘‘systematic errors’’ in skin-mark–based setups, whereas Fatunase et al. ‘‘did not observe systematic errors (our mean error was \1 mm).’’ There is more than one current usage for the term ‘‘systematic error.’’ One usage (patient-specific systematic error) refers to a setup error that persists in magnitude and direction throughout the treatment course of an individual patient. The other usage (group or process systematic error) refers to a setup error that is common to an entire patient population. The problem is that neither study qualifies or defines their use of the term ‘‘systematic error,’’ and it appears that White et al. use the term in the former sense whereas Fatunase et al. use it in the latter. In actuality, the results of the two studies appear consistent. In their paper White et al. state, ‘‘The mean of all means for both setup methods was \1 mm.’’ It is this result that Fatunase et al. should have compared with their own finding of no [group or process] systematic error. On the flip side, White et al.’s ‘‘systematic error’’ appears to refer to the standard deviation of individual patient mean setup errors (S), assuming that they are following van Herk (3), whom they cite in their paper. If one computes this same quantity from the data presented by Fatunase et al., one obtains 1.9, 2.5, and 2.0 mm in the right–left, anterior–posterior, and superior–inferior directions, respectively. This compares well with the White et al. published values of 2.7, 1.7, and 2.4 mm. Authors and reviewers are advised to be wary of indiscriminate use of the term ‘‘systematic error’’ (as well as ‘‘random error’’). They may refer to different quantities, depending on whether one is speaking within a global or patient-specific context. To avoid ambiguity and confusion, such terms should always be defined mathematically within any given study.
MARTIN KLEIN, PH.D. Department of Medical Psychology JAAP C. REIJNEVELD, M.D., PH.D. JAN J. HEIMANS, M.D., PH.D. Department of Neurology VU University Medical Center Amsterdam, The Netherlands doi:10.1016/j.ijrobp.2007.09.031 1. van Beek AP, van den Bergh AC, van den Berg LM, et al. Radiotherapy is not associated with reduced quality of life and cognitive function in patients treated for nonfunctioning pituitary adenoma. Int J Radiat Oncol Biol Phys 2007;68:986–991. 2. Cull A, Hay C, Love SB, et al. What do cancer patients mean when they complain of concentration and memory problems? Br J Cancer 1996;74: 1674–1679. 3. Newman S, Klinger L, Venn G, et al. Subjective reports of cognition in relation to assessed cognitive performance following coronary artery bypass surgery. J Psychosom Res 1989;33:227–233. 4. Khatri P, Babyak M, Clancy C, et al. Perception of cognitive function in older adults. Health Psychol 1999;18:301–306.
LEONARD KIM, M.S., A.MUS.D. Department of Radiation Oncology William Beaumont Hospital Royal Oak, MI doi:10.1016/j.ijrobp.2007.10.035 961