- Email: [email protected]
Evaluation of long-term effects of radiotherapy
Letters to the Editor / Radiotherapy and Oncology 99 (2011) 97–100
Leena Kankaanranta Kauko Saarilahti Department of Oncology, Helsinki University Central Hospital (HUCH), Helsinki, Finland Antti Mäkitie Department of Otolaryngology, Helsinki University Central Hospital (HUCH), Helsinki, Finland Petteri Välimäki Boneca Corporation, Helsinki, Finland Mikko Tenhunen Heikki Joensuu Department of Oncology, Helsinki University Central Hospital (HUCH), Helsinki, Finland E-mail addresses: heikki.joensuu@hus.fi (H. Joensuu) Received 26 January 2011 Received in revised form 3 February 2011 Accepted 10 February 2011
Selection bias potentially overestimates risk of breast pain from radiotherapy To the Editor, A recent article by Lundstedt et al. in the Journal Radiotherapy and Oncology compared the long term symptoms of women who were randomized in a Swedish multi-institutional trial to breast conserving surgery with or without postoperative radiotherapy [1]. This study is important, and certainly adds information to the literature that has the potential to improve the decision making process for patients and clinicians. This analysis by Lundstedt et al. suggests that there is an absolute increased risk of long term breast pain of 15.9%, with an associated relative risk of 1.80, based on 335 patients that met their eligibility criteria [1]. However, concern arises from the apparent selection bias in this study, which not only limits generalizability (i.e. external validity), but also poses a threat to the internal validity of comparisons between radiotherapy and non-radiotherapy arms [2]. Of minor concern is their choice to exclude patients born before 1931, thereby limiting the ability to generalize these results to elderly patients. Of much larger concern is their decision to exclude patients who have recurred, since there is an imbalance in these outcomes between the two treatment arms and an association between recurrence and the outcome of interest, breast pain [1,3]. Therefore, this analysis likely underestimates the risk of pain and use of analgesics in the non-radiotherapy arm, thereby over-estimating the difference between the relative risks of breast pain in the treatment arms. Of note, the authors appeared to have insight into this problematic analysis, as indicated by their comment in the discussion: ‘‘Still, in this study the comparisons between the treatment arms were not truly randomised comparisons, since the patients were selected as alive and recurrence free.’’ [1]. In addition, excluding the relatively large number of patients (246) who have died or recurred limits the clinical utility [1]. The only way to appropriately quote these numbers to a new patient making a decision between postoperative adjuvant radiotherapy versus observation is to state: ‘‘If after 10 years you do not die or have a recurrence, then you will have almost two times the risk of breast pain, if you choose radiotherapy’’. It would be more useful to quote the risk of pain, whether or not they have re-
99
curred, since clinicians cannot possibly know an individual patient’s outcome in ten years. Despite this limitation, the authors should be applauded for the merits of this study. Most notably, the long term health related quality of life outcomes measured in this study are certainly of great interest to patients, clinicians, and researchers. However, this analysis would have been strengthened by including the patients who died or recurred, in order to provide an accurate estimate of the risk of these important symptoms, and to facilitate the shared decision making process between women with breast cancer and their physicians. References [1] Lundstedt D, Gustafsson M, Malmstrom P, et al. Symptoms 10–17 years after breast cancer radiotherapy data from the randomised SWEBCG91-RT trial. Radiother Oncol 2010;97:281–7. [2] Berk RA. An introduction to sample selection bias in sociological data. Am Sociol Rev 1983;48:386–98. [3] Clarke M, Collins R, Darby S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15year survival: an overview of the randomised trials. Lancet 2005;366: 2087–106.
Robert Anton Olson BC Cancer Agency, Department of Radiation Oncology, 600 West 10th Ave., Vancouver, BC, Canada V5Z4E6 University of British Columbia, Division of Radiation Oncology and Developmental Radiotherapeutics, Canada Harvard School of Public Health, Department of Epidemiology, USA E-mail addresses: [email protected]
Evaluation of long-term effects of radiotherapy
To the Editor We thank Dr. Olson for the comment and for clarifying that we have evaluated the long-term effects of radiotherapy and nothing else. We hypothesized radiotherapy, in the long term, to be associated with one or several of eight symptom groups [1]. However, the effect measure was near unity for six symptom groups. Clear effects were seen for pain in the breast and disturbances of skin sensation. The wording to the patient by Dr. Olson, explaining our results, is absolutely correct. We did not approach women with recurrences. When weighing in symptoms produced by local recurrences in the clinical decision-making, physicians must get the information from other data sets than ours. Our planned next step is to find means for developing a completely, in the long term, atoxic tangential radiotherapy for breast cancer. Our findings say we need to find dose volume-effects for pain in the breast and disturbances of skin sensation to reach that goal. If we do not exceed the doses to relevant risk structures delivered 1991 and 1997 to the women in our study, we probably do not have to worry about erysipelas, heart symptoms, lung symptoms, rib fractures, edema or decreased shoulder mobility as late effects of the radiotherapy. Reference [1] Lundstedt D, Gustafsson M, Malmstrom P, et al. Symptoms 10–17 years after breast cancer radiotherapy data from the randomised SWEBCG91-RT trial. Radiother Oncol 2010;97:281–7.
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Letters to the Editor / Radiotherapy and Oncology 99 (2011) 97–100
Dan Lundstedt Gunnar Steineck Department of Oncology, Onkologiskt Centrum, Sahlgrenska University Hospital, Gothenburg, Sweden Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sweden E-mail addresses: [email protected] (D. Lundstedt)
Per Karlsson Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden
Leena Kankaanranta Kauko Saarilahti Department of Oncology, Helsinki University Central Hospital (HUCH), Helsinki, Finland Antti Mäkitie Department of Otolaryngology, Helsinki University Central Hospital (HUCH), Helsinki, Finland Petteri Välimäki Boneca Corporation, Helsinki, Finland Mikko Tenhunen Heikki Joensuu Department of Oncology, Helsinki University Central Hospital (HUCH), Helsinki, Finland E-mail addresses: heikki.joensuu@hus.fi (H. Joensuu) Received 26 January 2011 Received in revised form 3 February 2011 Accepted 10 February 2011
Selection bias potentially overestimates risk of breast pain from radiotherapy To the Editor, A recent article by Lundstedt et al. in the Journal Radiotherapy and Oncology compared the long term symptoms of women who were randomized in a Swedish multi-institutional trial to breast conserving surgery with or without postoperative radiotherapy [1]. This study is important, and certainly adds information to the literature that has the potential to improve the decision making process for patients and clinicians. This analysis by Lundstedt et al. suggests that there is an absolute increased risk of long term breast pain of 15.9%, with an associated relative risk of 1.80, based on 335 patients that met their eligibility criteria [1]. However, concern arises from the apparent selection bias in this study, which not only limits generalizability (i.e. external validity), but also poses a threat to the internal validity of comparisons between radiotherapy and non-radiotherapy arms [2]. Of minor concern is their choice to exclude patients born before 1931, thereby limiting the ability to generalize these results to elderly patients. Of much larger concern is their decision to exclude patients who have recurred, since there is an imbalance in these outcomes between the two treatment arms and an association between recurrence and the outcome of interest, breast pain [1,3]. Therefore, this analysis likely underestimates the risk of pain and use of analgesics in the non-radiotherapy arm, thereby over-estimating the difference between the relative risks of breast pain in the treatment arms. Of note, the authors appeared to have insight into this problematic analysis, as indicated by their comment in the discussion: ‘‘Still, in this study the comparisons between the treatment arms were not truly randomised comparisons, since the patients were selected as alive and recurrence free.’’ [1]. In addition, excluding the relatively large number of patients (246) who have died or recurred limits the clinical utility [1]. The only way to appropriately quote these numbers to a new patient making a decision between postoperative adjuvant radiotherapy versus observation is to state: ‘‘If after 10 years you do not die or have a recurrence, then you will have almost two times the risk of breast pain, if you choose radiotherapy’’. It would be more useful to quote the risk of pain, whether or not they have re-
99
curred, since clinicians cannot possibly know an individual patient’s outcome in ten years. Despite this limitation, the authors should be applauded for the merits of this study. Most notably, the long term health related quality of life outcomes measured in this study are certainly of great interest to patients, clinicians, and researchers. However, this analysis would have been strengthened by including the patients who died or recurred, in order to provide an accurate estimate of the risk of these important symptoms, and to facilitate the shared decision making process between women with breast cancer and their physicians. References [1] Lundstedt D, Gustafsson M, Malmstrom P, et al. Symptoms 10–17 years after breast cancer radiotherapy data from the randomised SWEBCG91-RT trial. Radiother Oncol 2010;97:281–7. [2] Berk RA. An introduction to sample selection bias in sociological data. Am Sociol Rev 1983;48:386–98. [3] Clarke M, Collins R, Darby S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15year survival: an overview of the randomised trials. Lancet 2005;366: 2087–106.
Robert Anton Olson BC Cancer Agency, Department of Radiation Oncology, 600 West 10th Ave., Vancouver, BC, Canada V5Z4E6 University of British Columbia, Division of Radiation Oncology and Developmental Radiotherapeutics, Canada Harvard School of Public Health, Department of Epidemiology, USA E-mail addresses: [email protected]
Evaluation of long-term effects of radiotherapy
To the Editor We thank Dr. Olson for the comment and for clarifying that we have evaluated the long-term effects of radiotherapy and nothing else. We hypothesized radiotherapy, in the long term, to be associated with one or several of eight symptom groups [1]. However, the effect measure was near unity for six symptom groups. Clear effects were seen for pain in the breast and disturbances of skin sensation. The wording to the patient by Dr. Olson, explaining our results, is absolutely correct. We did not approach women with recurrences. When weighing in symptoms produced by local recurrences in the clinical decision-making, physicians must get the information from other data sets than ours. Our planned next step is to find means for developing a completely, in the long term, atoxic tangential radiotherapy for breast cancer. Our findings say we need to find dose volume-effects for pain in the breast and disturbances of skin sensation to reach that goal. If we do not exceed the doses to relevant risk structures delivered 1991 and 1997 to the women in our study, we probably do not have to worry about erysipelas, heart symptoms, lung symptoms, rib fractures, edema or decreased shoulder mobility as late effects of the radiotherapy. Reference [1] Lundstedt D, Gustafsson M, Malmstrom P, et al. Symptoms 10–17 years after breast cancer radiotherapy data from the randomised SWEBCG91-RT trial. Radiother Oncol 2010;97:281–7.
100
Letters to the Editor / Radiotherapy and Oncology 99 (2011) 97–100
Dan Lundstedt Gunnar Steineck Department of Oncology, Onkologiskt Centrum, Sahlgrenska University Hospital, Gothenburg, Sweden Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sweden E-mail addresses: [email protected] (D. Lundstedt)
Per Karlsson Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden