- Email: [email protected]
In Reply to Drs. Chen and Liang
1606
I. J. Radiation Oncology d Biology d Physics
extent in patients with the International Federation of Gynecology and Obstetrics (FIGO) Stage III cervical cancer. They also suggested that a tailored treatment policy for each subgroup should be considered. However, survival was mainly dependent on complete response (shown in the multivariate analysis). Many issues need to be discussed further from their study. First, we suggest that a novel classification strategy should be based on the records in the modern era because chemoradiotherapy (CCRT) has become a standard pattern of care. In this way, more appropriate treatment policies can be considered. Second, pelvic lymph node status was not demonstrated as a prognostic factor for survival in their analysis, which shows some discrepancy with the reports investigating risk stratification (2, 3). Also, it is problematic to draw the conclusion that the high-risk group (bilateral pelvic wall involvement with hydronephrosis) did poorly because the sample size was extremely small (n = 7). Finally, the high-dose-rate intracavitary brachytherapy (HDRICB) scheme should be optimized because the overall complete response rate was lower than that of the studies investigating CCRT plus HDRICB (4, 5). In our experience from 1994 through 2006, 103 patients with Stage III cervical cancer were reviewed. The standard dose was 45 Gy to the whole pelvis with a parametrial boost of 12.6–14 Gy, combined with four courses of HDRICB with a total prescribed dose of 24 Gy. The 5-year cause-specific survival (CSS) was 58% in the non-CCRT era and 67% in the CCRT era. The complete response rate was 93% when assessing at 1 month after radiotherapy. Multivariate analyses of the CSS revealed 2 prognostic factors: pelvic lymph node status and overall treatment time $63 days. Maximal tumor size $8 cm was demonstrated as the predictor for pelvic failure, whereas the prognostic factor for distant metastasis was lymph node status. Furthermore, our previous study showed pretreatment carcinoembryonic antigen levels $10 ng/mL predicted an inferior disease-free survival for patients with Stage III disease (6). Imaging studies and tumor markers are becoming increasingly common as pretreatment tumor parameters when irradiating advanced cervical cancer. We recommend reappraisal of FIGO Stage III tumors by integrating modern parameters, rather than using traditional information when performing risk stratification or treatment optimization. SHANG-WEN CHEN, M.D. Department of Radiation Oncology and School of Medicine China Medical University Hospital School of Medicine Taipei Medical University JI-AN LIANG, M.D. Department of Radiation Oncology and School of Medicine China Medical University Hospital doi:10.1016/j.ijrobp.2010.02.044 1. Kim YB, Lee IJ, Kim SY, et al. Tumor heterogeneity of FIGO Stage III carcinoma of the uterine cervix. Int J Radiation Oncology Biol Phys 2009;75:1323–1328. 2. Stehman FB, Bundy BN, DiSaia PJ, et al. Carcinoma of the cervix treated with radiotherapy. I. A multi-variate analysis of prognostic variables in the Gynecologic Oncology Group. Cancer 1991;67:2776–2785. 3. Hong JH, Tsai CS, Lai CH, et al. Risk stratification of patients with advanced squamous cell carcinoma of cervix treated by radiotherapy alone. Int J Radiol Oncol Biol Phys 2005;63:492–499. 4. Chen SW, Liang JA, Hung YC, et al. Concurrent weekly cisplatin plus external beam radiotherapy and high-dose rate brachytherapy for advanced cervical cancer: A control cohort comparison with radiation alone on treatment outcome and complications. Int J Radiat Oncol Biol Phys 2006;66:1370–1377. 5. Souhami L, Seymour R, Roman TN, et al. Weekly cisplatin plus external beam radiotherapy and high dose rate brachytherapy in patients with locally advanced carcinoma of the cervix. Int J Radiat Oncol Biol Phys 1993;27:871–878. 6. Chen SW, Liang JA, Hung YC, et al. The clinical implications of elevated pretreatment carcinoembryonic antigen in patients with advanced squamous cell carcinoma of the uterine cervix. Tumor Biol 2008;29: 255–261. IN REPLY TO DRS. CHEN AND LIANG To the Editor: We thank Drs. Chen and Liang for their interest in our recent publication (1). The incidence of uterine cervical cancer has rapidly decreased in the past 2 decades in Korea (2), and our data show a significant imbalance according to treatment year from 1986 to 2004. Half of the
Volume 77, Number 5, 2010 patients included in this analysis had been treated for the first 7 years, and \10% were enrolled after 2000. In this study, only 10% of patients received concurrent chemotherapy. As Drs. Chen and Liang indicated, the current treatment standard in locally advanced uterine cervical cancer has been radiotherapy with concurrent chemotherapy since the National Cancer Institute statement of 1999 (3). However, our data show that the key point to treatment success may depend on customizing radiotherapy according to tumor heterogeneity rather than untailored chemotherapy for International Federation of Gynecology and Obstetrics (FIGO) Stage III patients. As noted, patients with lymph node (LN) involvement have the worst prognosis, and our data show the same results without statistical significance. Because of the criterion for size on CT imaging in the Pre-PET/CT era, it has not been a satisfactory solution to evaluate LN metastasis, and FIGO staging did not adopt LN staging. In the future, LN metastasis may be one of the components to determine the prognosis of uterine cervical cancer. In our institution, we chose the initial treatment field of external beam radiotherapy according to location and number of LNs, and added LN boost (5.4–9 Gy) to the gross LN-bearing region. We suppose that such an aggressive treatment approach would suppress poor prognostic features. Our risk group stratification was based on the definition of FIGO Stage IIIb, such as pelvic wall extension, and hydronephrosis. As mentioned in the Discussion section, many investigators have developed a prognostic criterion according to tumor burden or hydronephrosis in uterine cervical cancers. Therefore, a revised edition of FIGO stage in uterine cervical cancer should reflect tumor heterogeneity of Stage IIIb and be refined according to the prognosis in the future. Thus far, few data exist regarding the complete remission (CR) rate in FIGO IIIb. In our study, acquisition of CR was not explained by any clinicopathological factors. Non-CR patients took 19%, 20.9%, and 71.4% in Subgroups 1, 2, and 3, respectively. The median overall treatment time (OTT, median 78 days) was somewhat longer. Effective supportive care, such as Granulocyte macrophage colony-stimulating factor, was not available in the 1980s and 1990s. OTT has no substantial impact on the CR rate, and no prognostic significance. However, in our institution, OTT is shortened within 60 days by protocol revision of the combination of external beam radiotherapy with Intracavitary radiation (4, 5). Tumor response to radiotherapy may be further explained by biological factors rather than clinicopathological factors (6–8). As indicated, the newest imaging technologies, such as MRI or PET-CT and tumor markers, can refine FIGO Stage III in addition to clinicopathological parameters. Continuous efforts to select significant factors should be made to develop a tailored treatment policy based on tumor heterogeneity for Stage III patients. YONG BAE KIM, M.D. Department of Radiation Oncology Yonsei Cancer Center, Severance Hospital Yonsei University College of Medicine Seoul, Korea GWI EON KIM, M.D. Department of Radiation Oncology Yonsei Cancer Center, Severance Hospital Yonsei University College of Medicine Seoul, Korea doi:10.1016/j.ijrobp.2010.02.045 1. Kim YB, Lee IJ, Kim SY, et al. Tumor heterogeneity of FIGO stage III carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys 2009;75: 1323–1328. 2. Jo H, Jeon YT, Hwang SY, et al. Increasing trend in the incidence of cervical cancer among the elderly in Korea: A population-based study from 1993 to 2002. Acta Oncol 2007;46:852–858. 3. NCI Clinical Announcement. Concurrent chemoradiation for cervical cancer. Washington, DC: National Cancer Institute, United States Department of Public Health; 1999. 4. Cho JH, Kim HC, Suh CO, et al. Optimum radiotherapy schedule for uterine cervical cancer based-on the detailed information of dose fractionation and radiotherapy technique. J Korean Soc Ther Rad Oncol 2005;23: 143–156. 5. Lee SW, Suh CO, Chung EJ, Kim GE. Dose optimization of fractionated external radiation and high-dose-rate intracavitary brachytherapy for FIGO Stage IB uterine cervical carcinoma. Int J Radiat Oncol Biol Phys 2002;52:1338–1344. 6. Kim YB, Kim GE, Cho NH, et al. Overexpression of cyclooxygenase-2 is associated with a poor prognosis in patients with squamous cell carcinoma
Letters to the Editor of the uterine cervix treated with radiation and concurrent chemotherapy. Cancer 2002;95:531–539. 7. Cho NH, Kim YB, Park TK, et al. P63 and EGFR as prognostic predictors in Stage IIB radiation-treated cervical squamous cell carcinoma. Gynecol Oncol 2003;91:346–353. 8. Kim YB, Kim GE, Pyo HR, et al. Differential cyclooxygenase-2 expression in squamous cell carcinoma and adenocarcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys 2004;60:822–829.
RATE OF SECONDARY MALIGNANCIES AFTER RADICAL PROSTATECTOMY VERSUS EXTERNAL BEAM RADIATION THERAPY FOR LOCALIZED PROSTATE CANCER (INT J RADIAT ONCOL BIOL PHYS 2010;76:342–348) To the Editor: Dr. Bhojani et al. (1) recently published a study evaluating second cancer rates in 17,845 patients treated with radical prostatectomy (RP) or external beam radiation therapy (EBRT). The retrospective, population-based design of this study makes it difficult to quantitate the effect of radiation on cancer rates, especially when comparing two populations of disparate ages and fitness levels. The mean age for RP patients was 5 years younger than the EBRT patient population, 64.6 and 69.6 years respectively. The older population is naturally expected to have higher cancer rates, but ‘‘adjustment for age’’ was not clarified. Were directly age-matched comparisons performed between the groups? If so, were differences as pronounced? Comparisons of cancer rates after 5 years are useful for ‘‘hypothesis testing,’’ but may be too early for purely radiation-induced cancers, which typically onset after a multi-year lag, but continue to increase with time. However, comparing 10-year and later cancer events, only lung cancer rates remained elevated, despite lung receiving little radiation during prostate radiotherapy, suggesting an alternative hypothesis. Smoking is major risk factor for lung cancer yet was unaccounted for in this study. Depending on prevalence, tobacco use alone could account for the observed 2.2% elevation in lung cancer rate seen in the EBRT group at 15 years. Smoking is also a risk factor for lung and heart disease, both possible contraindications for surgery. Thus, the EBRT population may be enriched with smokers and generally unhealthier patients, as they scored nearly twice as high as RP patients on the Charlson Comorbidity Index. Smoking also contributes to bladder and rectal cancers, which could partially explain these 5-year increased rates in EBRT patients. Is tobacco use available for subanalysis in this population database? In Hodgkin’s lymphoma survivors treated with chemotherapy and radiation, smoking increases the risk of lung cancer more than 20-fold. Radiation carcinogenesis is dose and time dependent but also often needs an accomplice, such as young patient age, alkylator chemotherapy, or tobacco (2). Short of a large randomized trial, evaluation of secondary cancer rates requires careful control of major known cancer risks. CHRISTIAN HYDE, M.D. Department of Radiation Oncology Intermountain Healthcare Saint George, Utah
1607 doi:10.1016/j.ijrobp.2010.03.025
1. Bhojani N, Capitanio U, Suardi N, et al. The rate of secondary malignancies after radical prostatectomy versus external beam radiation therapy for localized prostate cancer: a population based study on 17,845 patients. Int J Radiat Oncol Biol Phys 2010;76:342–348. 2. Travis LB, Gospodarowicz M, Curtis RE, et al. Lung cancer following radiotherapy and chemotherapy for Hodgkin’s disease. J Natl Cancer Inst 2002;194:182–192.
IN REPLY TO DR. HYDE We wish to thank Dr. Hyde for his interest and extremely pertinent comments. His concerns about the effect of cigarette smoking are well founded. It is possible that higher rates of tobacco exposure predisposed patients treated with radiotherapy to higher rates of lung cancer. Unfortunately, tobacco exposure cannot be controlled for in the database used for this analysis. In consequence, its effect as a potential confounder cannot be ruled out. Nonetheless, it may be argued that the effect of controlling for age and comorbidities (see multivariable analyses) does at least partially account for the effect of smoking. However, this assumption cannot be directly confirmed. In consequence, higher rates of lung cancer at 10 years after radiation therapy may be directly related to radiotherapy itself or may be due to other confounders, of which tobacco exposure represents an important candidate. NAEEM BHOJANI MAXINE SUN RODOLPHE THURET LARS BUDAEUS PIERRE I. KARAKIEWICZ Cancer Prognostics and Health Outcomes Unit University of Montreal Health Centre Montreal, Quebec, Canada H2X 3J4 doi:10.1016/j.ijrobp.2010.03.026
ERRATUM Re: Yoon S, Stangenberg L, Lee YJ, et al. Efficacy of Sunitinib and Radiotherapy in Genetically Engineered Mouse Model of Soft Tissue. Int J Radiat Oncol Biol Phys 2009;74:1207-1216. In the above-noted article, the first two authors, Sam S. Yoon, M.D. and Lars Stangenberg M.D. contributed equally to the writing of this paper. The published article did include such an attribution. doi:10.1016/j.ijrobp.2010.06.004
I. J. Radiation Oncology d Biology d Physics
extent in patients with the International Federation of Gynecology and Obstetrics (FIGO) Stage III cervical cancer. They also suggested that a tailored treatment policy for each subgroup should be considered. However, survival was mainly dependent on complete response (shown in the multivariate analysis). Many issues need to be discussed further from their study. First, we suggest that a novel classification strategy should be based on the records in the modern era because chemoradiotherapy (CCRT) has become a standard pattern of care. In this way, more appropriate treatment policies can be considered. Second, pelvic lymph node status was not demonstrated as a prognostic factor for survival in their analysis, which shows some discrepancy with the reports investigating risk stratification (2, 3). Also, it is problematic to draw the conclusion that the high-risk group (bilateral pelvic wall involvement with hydronephrosis) did poorly because the sample size was extremely small (n = 7). Finally, the high-dose-rate intracavitary brachytherapy (HDRICB) scheme should be optimized because the overall complete response rate was lower than that of the studies investigating CCRT plus HDRICB (4, 5). In our experience from 1994 through 2006, 103 patients with Stage III cervical cancer were reviewed. The standard dose was 45 Gy to the whole pelvis with a parametrial boost of 12.6–14 Gy, combined with four courses of HDRICB with a total prescribed dose of 24 Gy. The 5-year cause-specific survival (CSS) was 58% in the non-CCRT era and 67% in the CCRT era. The complete response rate was 93% when assessing at 1 month after radiotherapy. Multivariate analyses of the CSS revealed 2 prognostic factors: pelvic lymph node status and overall treatment time $63 days. Maximal tumor size $8 cm was demonstrated as the predictor for pelvic failure, whereas the prognostic factor for distant metastasis was lymph node status. Furthermore, our previous study showed pretreatment carcinoembryonic antigen levels $10 ng/mL predicted an inferior disease-free survival for patients with Stage III disease (6). Imaging studies and tumor markers are becoming increasingly common as pretreatment tumor parameters when irradiating advanced cervical cancer. We recommend reappraisal of FIGO Stage III tumors by integrating modern parameters, rather than using traditional information when performing risk stratification or treatment optimization. SHANG-WEN CHEN, M.D. Department of Radiation Oncology and School of Medicine China Medical University Hospital School of Medicine Taipei Medical University JI-AN LIANG, M.D. Department of Radiation Oncology and School of Medicine China Medical University Hospital doi:10.1016/j.ijrobp.2010.02.044 1. Kim YB, Lee IJ, Kim SY, et al. Tumor heterogeneity of FIGO Stage III carcinoma of the uterine cervix. Int J Radiation Oncology Biol Phys 2009;75:1323–1328. 2. Stehman FB, Bundy BN, DiSaia PJ, et al. Carcinoma of the cervix treated with radiotherapy. I. A multi-variate analysis of prognostic variables in the Gynecologic Oncology Group. Cancer 1991;67:2776–2785. 3. Hong JH, Tsai CS, Lai CH, et al. Risk stratification of patients with advanced squamous cell carcinoma of cervix treated by radiotherapy alone. Int J Radiol Oncol Biol Phys 2005;63:492–499. 4. Chen SW, Liang JA, Hung YC, et al. Concurrent weekly cisplatin plus external beam radiotherapy and high-dose rate brachytherapy for advanced cervical cancer: A control cohort comparison with radiation alone on treatment outcome and complications. Int J Radiat Oncol Biol Phys 2006;66:1370–1377. 5. Souhami L, Seymour R, Roman TN, et al. Weekly cisplatin plus external beam radiotherapy and high dose rate brachytherapy in patients with locally advanced carcinoma of the cervix. Int J Radiat Oncol Biol Phys 1993;27:871–878. 6. Chen SW, Liang JA, Hung YC, et al. The clinical implications of elevated pretreatment carcinoembryonic antigen in patients with advanced squamous cell carcinoma of the uterine cervix. Tumor Biol 2008;29: 255–261. IN REPLY TO DRS. CHEN AND LIANG To the Editor: We thank Drs. Chen and Liang for their interest in our recent publication (1). The incidence of uterine cervical cancer has rapidly decreased in the past 2 decades in Korea (2), and our data show a significant imbalance according to treatment year from 1986 to 2004. Half of the
Volume 77, Number 5, 2010 patients included in this analysis had been treated for the first 7 years, and \10% were enrolled after 2000. In this study, only 10% of patients received concurrent chemotherapy. As Drs. Chen and Liang indicated, the current treatment standard in locally advanced uterine cervical cancer has been radiotherapy with concurrent chemotherapy since the National Cancer Institute statement of 1999 (3). However, our data show that the key point to treatment success may depend on customizing radiotherapy according to tumor heterogeneity rather than untailored chemotherapy for International Federation of Gynecology and Obstetrics (FIGO) Stage III patients. As noted, patients with lymph node (LN) involvement have the worst prognosis, and our data show the same results without statistical significance. Because of the criterion for size on CT imaging in the Pre-PET/CT era, it has not been a satisfactory solution to evaluate LN metastasis, and FIGO staging did not adopt LN staging. In the future, LN metastasis may be one of the components to determine the prognosis of uterine cervical cancer. In our institution, we chose the initial treatment field of external beam radiotherapy according to location and number of LNs, and added LN boost (5.4–9 Gy) to the gross LN-bearing region. We suppose that such an aggressive treatment approach would suppress poor prognostic features. Our risk group stratification was based on the definition of FIGO Stage IIIb, such as pelvic wall extension, and hydronephrosis. As mentioned in the Discussion section, many investigators have developed a prognostic criterion according to tumor burden or hydronephrosis in uterine cervical cancers. Therefore, a revised edition of FIGO stage in uterine cervical cancer should reflect tumor heterogeneity of Stage IIIb and be refined according to the prognosis in the future. Thus far, few data exist regarding the complete remission (CR) rate in FIGO IIIb. In our study, acquisition of CR was not explained by any clinicopathological factors. Non-CR patients took 19%, 20.9%, and 71.4% in Subgroups 1, 2, and 3, respectively. The median overall treatment time (OTT, median 78 days) was somewhat longer. Effective supportive care, such as Granulocyte macrophage colony-stimulating factor, was not available in the 1980s and 1990s. OTT has no substantial impact on the CR rate, and no prognostic significance. However, in our institution, OTT is shortened within 60 days by protocol revision of the combination of external beam radiotherapy with Intracavitary radiation (4, 5). Tumor response to radiotherapy may be further explained by biological factors rather than clinicopathological factors (6–8). As indicated, the newest imaging technologies, such as MRI or PET-CT and tumor markers, can refine FIGO Stage III in addition to clinicopathological parameters. Continuous efforts to select significant factors should be made to develop a tailored treatment policy based on tumor heterogeneity for Stage III patients. YONG BAE KIM, M.D. Department of Radiation Oncology Yonsei Cancer Center, Severance Hospital Yonsei University College of Medicine Seoul, Korea GWI EON KIM, M.D. Department of Radiation Oncology Yonsei Cancer Center, Severance Hospital Yonsei University College of Medicine Seoul, Korea doi:10.1016/j.ijrobp.2010.02.045 1. Kim YB, Lee IJ, Kim SY, et al. Tumor heterogeneity of FIGO stage III carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys 2009;75: 1323–1328. 2. Jo H, Jeon YT, Hwang SY, et al. Increasing trend in the incidence of cervical cancer among the elderly in Korea: A population-based study from 1993 to 2002. Acta Oncol 2007;46:852–858. 3. NCI Clinical Announcement. Concurrent chemoradiation for cervical cancer. Washington, DC: National Cancer Institute, United States Department of Public Health; 1999. 4. Cho JH, Kim HC, Suh CO, et al. Optimum radiotherapy schedule for uterine cervical cancer based-on the detailed information of dose fractionation and radiotherapy technique. J Korean Soc Ther Rad Oncol 2005;23: 143–156. 5. Lee SW, Suh CO, Chung EJ, Kim GE. Dose optimization of fractionated external radiation and high-dose-rate intracavitary brachytherapy for FIGO Stage IB uterine cervical carcinoma. Int J Radiat Oncol Biol Phys 2002;52:1338–1344. 6. Kim YB, Kim GE, Cho NH, et al. Overexpression of cyclooxygenase-2 is associated with a poor prognosis in patients with squamous cell carcinoma
Letters to the Editor of the uterine cervix treated with radiation and concurrent chemotherapy. Cancer 2002;95:531–539. 7. Cho NH, Kim YB, Park TK, et al. P63 and EGFR as prognostic predictors in Stage IIB radiation-treated cervical squamous cell carcinoma. Gynecol Oncol 2003;91:346–353. 8. Kim YB, Kim GE, Pyo HR, et al. Differential cyclooxygenase-2 expression in squamous cell carcinoma and adenocarcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys 2004;60:822–829.
RATE OF SECONDARY MALIGNANCIES AFTER RADICAL PROSTATECTOMY VERSUS EXTERNAL BEAM RADIATION THERAPY FOR LOCALIZED PROSTATE CANCER (INT J RADIAT ONCOL BIOL PHYS 2010;76:342–348) To the Editor: Dr. Bhojani et al. (1) recently published a study evaluating second cancer rates in 17,845 patients treated with radical prostatectomy (RP) or external beam radiation therapy (EBRT). The retrospective, population-based design of this study makes it difficult to quantitate the effect of radiation on cancer rates, especially when comparing two populations of disparate ages and fitness levels. The mean age for RP patients was 5 years younger than the EBRT patient population, 64.6 and 69.6 years respectively. The older population is naturally expected to have higher cancer rates, but ‘‘adjustment for age’’ was not clarified. Were directly age-matched comparisons performed between the groups? If so, were differences as pronounced? Comparisons of cancer rates after 5 years are useful for ‘‘hypothesis testing,’’ but may be too early for purely radiation-induced cancers, which typically onset after a multi-year lag, but continue to increase with time. However, comparing 10-year and later cancer events, only lung cancer rates remained elevated, despite lung receiving little radiation during prostate radiotherapy, suggesting an alternative hypothesis. Smoking is major risk factor for lung cancer yet was unaccounted for in this study. Depending on prevalence, tobacco use alone could account for the observed 2.2% elevation in lung cancer rate seen in the EBRT group at 15 years. Smoking is also a risk factor for lung and heart disease, both possible contraindications for surgery. Thus, the EBRT population may be enriched with smokers and generally unhealthier patients, as they scored nearly twice as high as RP patients on the Charlson Comorbidity Index. Smoking also contributes to bladder and rectal cancers, which could partially explain these 5-year increased rates in EBRT patients. Is tobacco use available for subanalysis in this population database? In Hodgkin’s lymphoma survivors treated with chemotherapy and radiation, smoking increases the risk of lung cancer more than 20-fold. Radiation carcinogenesis is dose and time dependent but also often needs an accomplice, such as young patient age, alkylator chemotherapy, or tobacco (2). Short of a large randomized trial, evaluation of secondary cancer rates requires careful control of major known cancer risks. CHRISTIAN HYDE, M.D. Department of Radiation Oncology Intermountain Healthcare Saint George, Utah
1607 doi:10.1016/j.ijrobp.2010.03.025
1. Bhojani N, Capitanio U, Suardi N, et al. The rate of secondary malignancies after radical prostatectomy versus external beam radiation therapy for localized prostate cancer: a population based study on 17,845 patients. Int J Radiat Oncol Biol Phys 2010;76:342–348. 2. Travis LB, Gospodarowicz M, Curtis RE, et al. Lung cancer following radiotherapy and chemotherapy for Hodgkin’s disease. J Natl Cancer Inst 2002;194:182–192.
IN REPLY TO DR. HYDE We wish to thank Dr. Hyde for his interest and extremely pertinent comments. His concerns about the effect of cigarette smoking are well founded. It is possible that higher rates of tobacco exposure predisposed patients treated with radiotherapy to higher rates of lung cancer. Unfortunately, tobacco exposure cannot be controlled for in the database used for this analysis. In consequence, its effect as a potential confounder cannot be ruled out. Nonetheless, it may be argued that the effect of controlling for age and comorbidities (see multivariable analyses) does at least partially account for the effect of smoking. However, this assumption cannot be directly confirmed. In consequence, higher rates of lung cancer at 10 years after radiation therapy may be directly related to radiotherapy itself or may be due to other confounders, of which tobacco exposure represents an important candidate. NAEEM BHOJANI MAXINE SUN RODOLPHE THURET LARS BUDAEUS PIERRE I. KARAKIEWICZ Cancer Prognostics and Health Outcomes Unit University of Montreal Health Centre Montreal, Quebec, Canada H2X 3J4 doi:10.1016/j.ijrobp.2010.03.026
ERRATUM Re: Yoon S, Stangenberg L, Lee YJ, et al. Efficacy of Sunitinib and Radiotherapy in Genetically Engineered Mouse Model of Soft Tissue. Int J Radiat Oncol Biol Phys 2009;74:1207-1216. In the above-noted article, the first two authors, Sam S. Yoon, M.D. and Lars Stangenberg M.D. contributed equally to the writing of this paper. The published article did include such an attribution. doi:10.1016/j.ijrobp.2010.06.004