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Journal of Clinical Oncology, Vol 22, No 7 (April 1), 2004: pp. 1341-1342 © 2004 American Society of Clinical Oncology. DOI: 10.1200/JCO.2004.99.056
Impact on Outcome of Delay in Starting RadiotherapyDepartment of Radiation Oncology, Harvard Medical School, and Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, MA To the Editor: I agree with the general conclusion of the recent review article by Huang et al, in the February 1, 2003, issue of the Journal of Clinical Oncology, that untoward delays in initiating radiotherapy after surgery are likely to have an adverse effect on patient outcome.1 However, many patient-, tumor-, and treatment-related factors that they did not discuss seem likely to substantially modify the exact impact of the surgery-to-radiotherapy interval (SRI).2 I will focus here on a few examples illustrating the possible roles of radiotherapy dose and margin status. Some of the studies of breast cancer patients reviewed by Huang et al did not employ a "boost" dose. Higher doses might overcome much or all of the effect of prolonging the SRI on tumor control (albeit with a potentially increased risk of complications). In a study of 673 node-negative patients not receiving systemic therapy who were treated at the Joint Center for Radiation Therapy (JCRT; Boston, MA) from 1968 to 1985, all patients received a dose of 60 Gy or higher to the primary tumor site.3 (This article was referenced by Huang et al, but the data were not described in detail or included in their Figure 1.) The median length of follow-up in surviving patients was 100 months. Crude 5-year breast failure rates were 13% for the 282 patients with an SRI of 0 to 4 weeks (measured from the date of the last breast surgery), 8% for 306 patients with an SRI of 5 to 8 weeks, and 2% for 54 patients with an SRI of 9 to 12 weeks. In a series of patients with head and neck cancers treated at Memorial Sloan-Kettering Cancer Center in New York, NY (included in their review, but not therein analyzed by radiation dose), patients receiving doses of less than 60 Gy had a risk of locoregional recurrence of 7% (3 of 41 patients) when the SRI was less than 6 weeks, compared with 27% (9 of 33 patients) when the SRI was longer.4 However, when doses of 60 Gy or higher were given, the failure rates in the early and delayed radiotherapy subgroups were 15% (3 of 20 patients) and 12% (2 of 17 patients), respectively.
In the JCRT randomized trial of the sequencing of chemotherapy and radiotherapy, margin status played a key role in the impact of treatment sequencing on local failure.5 At a median follow-up of 58 months, the crude 5-year failure rates in the radiotherapy-first and chemotherapy-first arms, respectively, according to margin status were as follows: unknown margin status, 0% v 20% (13 and 10 patients, respectively); positive margins, 14% v 25% (14 and 24 patients, respectively); "close" margins (tumor Although the numbers of patients in the subgroups discussed above were small, it seems quite plausible that radiation dose and margin status (probably the best available surrogate for the residual tumor burden following surgery) would modulate the impact of the SRI. However, their exact effects in specific contexts remain poorly delineated. (One obstacle to better understanding of the SRI is that the exact tumor-free margin width generally has not been recorded for patients in trials performed by cooperative oncology groups, nor in many single-institution retrospective databases.) I believe that the complex details of the interactions of the SRI with other parameters must be better understood to design optimal programs of surgery, chemotherapy, and radiotherapy for individual patient subgroups with different cancers. I hope that the excellent work of Huang et al will inspire more investigations of this critical subject. Author's Disclosures of Potential Conflicts of Interest The author 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. Recht A, Come SE: The optimal sequence of radiation therapy and chemotherapy in patients with early and locally advanced breast cancer. Semin Breast Dis 2:135-144, 1999 3. 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 radiotherapy without systemic therapy. Int J Radiat Oncol Biol Phys 30:17-21, 1994[Medline] 4. Schiff PB, Harrison LB, Strong EW, et al: Impact of the time interval between surgery and postoperative radiation therapy on locoregional control in advanced head and neck cancer. J Surg Oncol 43:203-208, 1990[Medline]
5. 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 6. Bellon J, Come SE, Gelman R, et al: Sequencing of chemotherapy and radiation therapy for patients with early stage breast cancer: Updated results of a prospective randomized trial. Int J Radiat Oncol Biol Phys 51:2-3, 2001 (abstr, suppl 1) 7. 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]
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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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1 mm from the inked edge), 0% v 23% (15 and 13 patients); and "negative" margins (> 1 mm), 16% v 0% (36 and 35 patients). (The results of this trial have recently been updated and presented in part,
