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In response to Dr. Formenti et al. (Int J Radiat Oncol Biol Phys 2005, 63:1275–1276)
Int. J. Radiation Oncology Biol. Phys., Vol. 64, No. 2, p. 658, 2006 Copyright © 2006 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/06/$–see front matter
LETTER TO THE EDITOR IN RESPONSE TO DR. FORMENTI ET AL. (INT J RADIAT ONCOL BIOL PHYS 2005, 63:1275–1276).
We agree that the optimal radiation dose to be given with concomitant chemotherapy for breast cancer is unknown. Although concurrent chemotherapy may result in greater acute toxicity during radiation, there is no evidence that delivering full radiation doses adversely impacts the delivery of dose-intense adjuvant chemotherapy. However, we hope that our investigation, along with the investigations of Dr. Formenti and her colleagues, will stimulate future studies that may eventually address the issue of radiation dose.
To the Editor: We thank Dr. Formenti for her interest in our novel approach to locally advanced breast cancer (1, 2). Formenti et al. have significant experience using concomitant paclitaxel and radiation therapy in a once-daily radiation schedule (3). In the era of widespread use of mammographic screening, locally advanced or inflammatory breast cancer is an uncommon presentation of breast cancer. The 16 patients in our study with Stage IIIB–C breast cancer were accrued over a period of slightly over seven years. Our trials were dose-escalation studies, and the results are descriptive at this point. Because of limitations of statistical power, we elected not to perform subset analyses on chemotherapy-naive patients. Of the 11 chemotherapy-naive patients, 8 were treated with paclitaxel alone, and 3 were treated with vinorelbine and paclitaxel. Six of these 11 patients achieved a pathologic complete response (pCR). At present, there is no clear consensus definition of pCR in the setting of posttreatment changes associated with locally advanced breast cancer (4). In our study, patients with no residual invasive breast cancer were classified as having a complete response. Residual tumor cells with extensive necrosis and/or pyknotic nuclei with chromatin condensation were considered “nonviable.” We chose not to define a “near” pathologic complete response. Our study was not powered to address the significance of partial or complete pathologic responses on disease-free survival. We agree that if the patients were to be analyzed using intent to treat principles, the denominator should be 16 rather than 15. For the pCR end point, the authors feel that the patient who died of a motor vehicle accident should not be counted as a failure, especially because she had an excellent clinical response before her untimely death. However, all survival end points were analyzed using intent to treat principles. We applaud Dr. Formenti’s group on their continued interest in locally advanced breast cancer as outlined in her letter to the editor. It should be noted that in Dr. Formenti’s study, 66% of patients had stage IIB–IIIA disease, whereas all ours had unresectable IIIB–IIIC disease (3).
JOHNNY KAO, M.D. SUZANNE CONZEN, M.D. GINI FLEMING, M.D. WENDY RECANT, M.D. RUTH HEIMANN, M.D., PH.D. University of Chicago Chicago, IL doi:10.1016/j.ijrobp.2005.09.029 1. Formenti SC. In regard to Kao et al.: Concomitant radiation therapy and paclitaxel for unresectable locally advanced breast cancer: Results from two consecutive phase I/II trials (Int J Radiat Oncol Biol Phys 2005; 61:1045–1053) [Letter]. Int J Radiat Oncol Biol Phys 2005;63:1275– 1276. 2. Kao J, Conzen SD, Jaskowiak NT, et al. Concomitant radiation therapy and paclitaxel for unresectable locally advanced breast cancer: Results from two consecutive phase I/II trials. Int J Radiat Oncol Biol Phys 2005;61:1045–1053. 3. Formenti SC, Volm M, Skinner KA, et al. Preoperative twice-weekly paclitaxel with concurrent radiation therapy followed by surgery and postoperative doxorubicin-based chemotherapy in locally advanced breast cancer: A phase I/II trial. J Clin Oncol 2003;21:864 – 870. 4. Ogston KN, Miller ID, Payne S, et al. A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast 2003;12:320 –327.
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LETTER TO THE EDITOR IN RESPONSE TO DR. FORMENTI ET AL. (INT J RADIAT ONCOL BIOL PHYS 2005, 63:1275–1276).
We agree that the optimal radiation dose to be given with concomitant chemotherapy for breast cancer is unknown. Although concurrent chemotherapy may result in greater acute toxicity during radiation, there is no evidence that delivering full radiation doses adversely impacts the delivery of dose-intense adjuvant chemotherapy. However, we hope that our investigation, along with the investigations of Dr. Formenti and her colleagues, will stimulate future studies that may eventually address the issue of radiation dose.
To the Editor: We thank Dr. Formenti for her interest in our novel approach to locally advanced breast cancer (1, 2). Formenti et al. have significant experience using concomitant paclitaxel and radiation therapy in a once-daily radiation schedule (3). In the era of widespread use of mammographic screening, locally advanced or inflammatory breast cancer is an uncommon presentation of breast cancer. The 16 patients in our study with Stage IIIB–C breast cancer were accrued over a period of slightly over seven years. Our trials were dose-escalation studies, and the results are descriptive at this point. Because of limitations of statistical power, we elected not to perform subset analyses on chemotherapy-naive patients. Of the 11 chemotherapy-naive patients, 8 were treated with paclitaxel alone, and 3 were treated with vinorelbine and paclitaxel. Six of these 11 patients achieved a pathologic complete response (pCR). At present, there is no clear consensus definition of pCR in the setting of posttreatment changes associated with locally advanced breast cancer (4). In our study, patients with no residual invasive breast cancer were classified as having a complete response. Residual tumor cells with extensive necrosis and/or pyknotic nuclei with chromatin condensation were considered “nonviable.” We chose not to define a “near” pathologic complete response. Our study was not powered to address the significance of partial or complete pathologic responses on disease-free survival. We agree that if the patients were to be analyzed using intent to treat principles, the denominator should be 16 rather than 15. For the pCR end point, the authors feel that the patient who died of a motor vehicle accident should not be counted as a failure, especially because she had an excellent clinical response before her untimely death. However, all survival end points were analyzed using intent to treat principles. We applaud Dr. Formenti’s group on their continued interest in locally advanced breast cancer as outlined in her letter to the editor. It should be noted that in Dr. Formenti’s study, 66% of patients had stage IIB–IIIA disease, whereas all ours had unresectable IIIB–IIIC disease (3).
JOHNNY KAO, M.D. SUZANNE CONZEN, M.D. GINI FLEMING, M.D. WENDY RECANT, M.D. RUTH HEIMANN, M.D., PH.D. University of Chicago Chicago, IL doi:10.1016/j.ijrobp.2005.09.029 1. Formenti SC. In regard to Kao et al.: Concomitant radiation therapy and paclitaxel for unresectable locally advanced breast cancer: Results from two consecutive phase I/II trials (Int J Radiat Oncol Biol Phys 2005; 61:1045–1053) [Letter]. Int J Radiat Oncol Biol Phys 2005;63:1275– 1276. 2. Kao J, Conzen SD, Jaskowiak NT, et al. Concomitant radiation therapy and paclitaxel for unresectable locally advanced breast cancer: Results from two consecutive phase I/II trials. Int J Radiat Oncol Biol Phys 2005;61:1045–1053. 3. Formenti SC, Volm M, Skinner KA, et al. Preoperative twice-weekly paclitaxel with concurrent radiation therapy followed by surgery and postoperative doxorubicin-based chemotherapy in locally advanced breast cancer: A phase I/II trial. J Clin Oncol 2003;21:864 – 870. 4. Ogston KN, Miller ID, Payne S, et al. A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast 2003;12:320 –327.
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