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Journal of Clinical Oncology, Vol 22, No 7 (April 1), 2004: pp. 1342-1343 © 2004 American Society of Clinical Oncology. DOI: 10.1200/JCO.2004.99.066
Delay of Radiation Therapy and Outcomes of Breast Cancer
Institut national de santé publique du Québec, Montreal, Québec, Canada To the Editor: We have read with great interest the recent publication by Huang et al1 concerning the impact of delaying radiation therapy on outcomes of tumors of the breast, head and neck region, and other sites. Having recently published a critical appraisal of the available evidence on the consequences of delay of radiotherapy for breast cancer,2 we would like to comment on this portion of Huang et al's paper. We were surprised not to find in Huang et al's analysis five publications included in our review,3-7 especially since in two, data represent higher-level evidence.3,4 The study by Nixon et al5 was excluded on the basis that definition of delay differed from the norm for breast cancer, but in fact these authors presented results for intervals of less than 5, 5 to 8, and 9 to 12 weeks, which seems compatible with other reports. In addition, some estimates in Figure 28-10 are derived from subset analyses of patients receiving both chemotherapy and radiation therapy in larger series of cases where the effect of delay to radiation was evaluated. Data on patients receiving radiation therapy but no chemotherapy in these same studies were ignored. For instance, Leonard et al8 reported local relapse-free survival of 95%, 94%, 100%, and 100% after delays of less than 1 month, at least 1 month but less than 3 months, at least 3 months but less than 6 months, and more than 6 months, respectively, in patients who did not receive chemotherapy; this finding should be included among those presented in Figure 1. Finally, information published only as an abstract is unsuitable for this kind of synthesis, since it provides no indication of the robustness of the research from which it is derived, for the investigator as well as for the reader. In Huang et al's paper, this concerns 2,522 patients of the 8,230 included in the analysis. Because the vast majority of these studies are observational, confounding by indication is a major problem, as recognized by the authors. Therefore, adjustment for factors likely to influence delay to radiation therapy and/or associated with outcomes of disease—especially margin status, advanced disease, or cotreatment—is absolutely essential. In fact, as shown in our review, in several cases, significant associations disappeared after adjustment for these covariates or interaction was observed.11-14 It is unclear how this source of bias might have influenced overall results since even using the best available estimate of effect for each study, some authors reported only crude measures of association. In recent years, delay in access to radiation therapy has been highly publicized. On compassionate grounds alone, treatment for cancer should always be initiated as early as possible after diagnosis. However, we believe that at least with respect to breast cancer, firm evidence concerning a specific delay that would have a detrimental effect on outcomes is still lacking, despite this ambitious work by Huang et al. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
1. Huang J, Barbera L, Brouwers M, et al: Does delay in starting treatment affect the outcomes of radiotherapy?. A systematic review. J Clin Oncol 21:555-563, 2003 2. Hébert-Croteau N, Freeman C, Latreille J, et al: Delay in adjuvant radiation treatment and outcomes of breast cancer: A review. Breast Cancer Res Treat 74:77-94, 2002[CrossRef][Medline] 3. Fisher B, Brown AM, Dimitrov NV, et al: Two months of doxorubicin-cyclophosphamide with and without reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: Results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol 8:1483-1496, 1990[Abstract] 4. Wallgren A, Bernier J, Gelber RD, et al: Timing of radiotherapy and chemotherapy following breast conserving surgery for patients with node-positive breast cancer. Int J Radiat Oncol Biol Phys 35:649-659, 1996[CrossRef][Medline] 5. Nixon AJ, Recht A, Neuberg D, et al: The relation between the surgery-radiotherapy interval and treatment outcome in patients treated with breast-conserving surgery and radiation therapy without systemic therapy. Int J Radiat Oncol Biol Phys 30:17-21, 1994[Medline] 6. Nguyen TD, Naja A, Chaplain G, et al: Influence du délai entre la chirurgie et l'irradiation locorégionale sur l'évolution des cancers du sein N+ non métastatiques: Une étude du Groupe des radiothérapeutes de la Fédération nationale des centres de lutte contre le cancer. Bull Cancer Radiother 80:229-233, 1993 7. Metz JM, Schultz D, Fox K, et al: Analysis of outcomes for high-risk breast cancer based on interval from surgery to postmastectomy radiation therapy. Cancer J 6:324-330, 2000[Medline] 8. Leonard CE, Wood ME, Zhen B, et al: Does administration of chemotherapy before radiotherapy in breast cancer patients treated with conservative surgery negatively impact local control?. J Clin Oncol 13:2906-2915, 1995[Abstract]
9. Meek AG, Park TL, Weiss TA, et al: Effect of delayed radiation therapy on local control in breast conservation therapy. Radiology 200:615-619, 1996 10. McCormick B, Norton L, Yao TJ, et al: The impact of the sequence of radiation and chemotherapy on local control after breast-conserving surgery. Cancer J Sci Am 2:39-45, 1996[Medline] 11. Clarke DH, Lê MG, Sarrazin D, et al: Analysis of loco-regional relapses in patients with early breast cancers treated by excision and radiotherapy: Experience of the Institut Gustave-Roussy. Int J Radiat Oncol Biol Phys 11:137-145, 1985[Medline] 12. Hartsell WF, Recine DC, Griem KL, et al: Delaying the initiation of intact breast irradiation for patients with lymph node positive breast cancer increases the risk of local recurrence. Cancer 76:2497-2503, 1995[CrossRef][Medline] 13. Froud PJ, Mates D, Jackson JSH, et al: Effect of time interval between breast-conserving surgery and radiation therapy on ipsilateral breast recurrence. Int J Radiat Oncol Biol Phys 46:363-372, 2000[CrossRef][Medline]
14. Recht A, Come SE, Henderson IC, et al: The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer. N Engl J Med 334:1356-1361, 1996
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Copyright © 2004 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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