|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
© 2000 American Society for Clinical Oncology Cost-Effectiveness of Adding an Electron-Beam Boost to Tangential Radiation Therapy in Patients With Negative Margins After Conservative Surgery for Early-Stage Breast CancerFrom the Department of Radiation Oncology, University of Michigan, Ann Arbor, MI; Department of Internal Medicine, Medical College of Virginia Campus of the Virginia Commonwealth University, Richmond, VA; Department of Radiation Oncology, Brigham and Women’s Hospital and Dana-Farber Cancer Institute; and Center for Outcomes and Policy Research, Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA. Address reprint requests to James A. Hayman, MD, Department of Radiation Oncology, University of Michigan Medical Center, UH B2C490, Box 0010, 1500 East Medical Center Dr, Ann Arbor, MI, 48109-0010; email hayman{at}umich.edu
PURPOSE: Electron-beam boosts (EBB) are routinely added after conservative surgery and tangential radiation therapy (TRT) for early-stage breast cancer. We performed an incremental cost-utility analysis to evaluate their cost-effectiveness. METHODS: A Markov model examined the impact of adding an EBB to TRT from a societal perspective. Outcomes were measured in quality-adjusted life years (QALYs). On the basis of the Lyon trial, the EBB was assumed to reduce local recurrences by approximately 2% at 10 years but to have no impact on survival. Patients’ utilities were used to adjust for quality of life. Given the small absolute benefit of the EBB, baseline utilities were assumed to be the same with or without it, an assumption evaluated by Monte Carlo simulation. Direct medical, time, and travel costs were considered. RESULTS: Adding the EBB led to an additional cost of $2,008, an increase of 0.0065 QALYs and, therefore, an incremental cost-effectiveness ratio of over $300,000/QALY. In a sensitivity analysis, the ratio was moderately sensitive to the efficacy and cost of the EBB and highly sensitive to patients’ utilities for treatment without it. Even if patients do value a small risk reduction, the mean cost-effectiveness ratio estimated by the Monte Carlo simulation remains high, at $70,859/QALY (95% confidence interval, $53,141 to $105,182/QALY). CONCLUSION: On the basis of currently available data, the cost-effectiveness ratio for the EBB is well above the commonly cited threshold for cost-effective care ($50,000/QALY). The EBB becomes cost-effective only if patients place an unexpectedly high value on the small absolute reduction in local recurrences achievable with it.
IT IS WELL ACCEPTED that breast-conserving surgery followed by radiation therapy and mastectomy have comparable survival rates when they are undertaken for the treatment of early-stage breast cancer. For women who desire breast preservation, it is standard practice to recommend treatment with radiation therapy after their breast-conserving surgery. Although the impact of radiation therapy on overall survival is uncertain, several randomized trials have clearly demonstrated that the addition of radiation therapy in this setting significantly decreases the risk of a local recurrence,1-5 thereby improving patients’ quality of life by decreasing their fear, as well as the actual likelihood, that they would experience a local recurrence, which could result in the loss of their breast.6 Treatment with radiation therapy after breast-conserving surgery begins with treatment to the entire breast. This is typically accomplished by using photons generated by a linear accelerator to treat tangential fields designed to include the whole breast. In general, a dose of 45 to 50 Gy is administered in divided doses given daily, Monday through Friday, over 5 weeks. In the United States, where less extensive surgery is commonly performed (ie, lumpectomy), it is then customary for patients to receive a radiation "boost" to the tumor bed region after they complete treatment with the tangent photon fields.7-9 The rationale for adding the boost is based on the theory that a higher rate of local control will be achieved if a higher dose of radiation is administered to the region of the breast thought to have the greatest tumor burden. In an attempt to increase the dose without significantly increasing the risk of a local complication, treatment techniques that limit the high-dose region are commonly used for the boost. Although the use of interstitial brachytherapy was not uncommon in the past, it has been replaced in most centers by the use of a short course of fractionated treatment using an electron beam generated by a linear accelerator. While the use of an electron beam boost does result in additional treatment planning costs and, like the tangential-fields treatment, is also given daily, Monday through Friday, it generally only extends the length of treatment by 1 to 2 weeks. The issue of whether or not all patients should receive a boost after completing their tangential radiation therapy is controversial.10-12 A number of retrospective series in which lumpectomy margins either were not assessed or were "close" have suggested that the addition of the boost reduces the risk of a local recurrence, and these studies have recommended its use in this setting.13-15 In contrast, in patients with negative margins after lumpectomy, three retrospective studies have reported excellent results without the boost.13-16 Perhaps the most commonly cited study by those practitioners who oppose the boost is the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-06 trial.2 This trial randomized women with early-stage breast cancer to treatment with lumpectomy alone, lumpectomy and radiation therapy, or mastectomy. All patients treated on the lumpectomy and radiation therapy arm of the study were required to have negative margins and only received tangential radiation therapy without a boost. Opponents of the boost point out that the local recurrence rate for the lumpectomy and radiation therapy arm of the B-06 trial seems to be similar to the rates reported by many institutions that routinely use a boost.7-9 In an attempt to resolve this issue, a prospective randomized trial was conducted in Lyon, France, in which 1,024 patients with early-stage breast cancers were treated with lumpectomy, axillary dissection, and tangential radiation therapy to the entire breast and were then randomized to either no further treatment or treatment with an electron-beam boost.17 All patients were required to have negative margins. With a median follow-up period of 3.3 years, the authors reported that the addition of the boost resulted in a 20% reduction in the actuarial local recurrence rate at 5 years (4.5% v 3.6%, P = .044), but that it appears to have no impact on overall survival. Nevertheless, on the basis of the statistically significant reduction in local recurrence rate, the authors seem to advocate the use of an electron-beam boost in patients with negative margins. In the past, an intervention in oncology was usually adopted into clinical practice if it could be demonstrated that it significantly improved survival and/or, more recently, patients’ quality of life. However, an additional question is increasingly being asked: is the magnitude of the treatment’s benefit sufficient to justify its cost (ie, is it cost-effective)? To investigate whether or not the use of an electron-beam boost is cost-effective in patients with negative margins, we created a Markov decision-analytic model designed to estimate the costs and benefits of treatment with and without a boost.
The cost-effectiveness of adding an electron-beam boost to tangential radiation therapy after conservative surgery for early-stage breast cancer was evaluated by comparing the associated costs and benefits of two competing treatment strategies: treatment with an electron-beam boost versus treatment without it. This was accomplished by modifying an existing Markov model constructed to evaluate the cost-effectiveness of adding any radiation therapy after breast-conserving surgery.18 As in our previous model, this model followed a hypothetical cohort of 60-year-old patients with early-stage breast cancer who had chosen breast-conserving therapy for 10 years. During each yearly cycle, the model estimated the costs and quality-adjusted life years (QALYs) associated with each treatment strategy. QALYs are essentially the area under the curve when survival is plotted against quality of life. They are calculated by multiplying the number of years spent in each relevant health state by the utility for that health state and then summing the products. Utilities are quality-of-life measures that estimate individuals’ preferences for given states of health and are generally measured on a scale ranging from 0 to 1, where 0 is defined as being equivalent to death and 1 as equivalent to optimal health. At the end of the 10-year period, the additional costs and benefits of the electron-beam boost were then summed and its cost-effectiveness assessed.
Baseline Model
The possible outcomes after the completion of treatment included being disease-free, experiencing a local recurrence, experiencing a systemic recurrence, or dying of breast cancer or of other causes. The model accounted for continued follow-up costs in patients who remained disease-free. Regardless of whether patients received the boost or not, the model assumed that all patients who experienced a local recurrence received salvage treatment with mastectomy and reconstructive surgery. The baseline model assumed that all patients who developed systemic recurrences underwent restaging and then went on to receive salvage chemotherapy. In the first year after systemic salvage treatment, patients would then either enter into a remission or die of breast cancer or of other causes. For patients who achieved remission, the model assumed that they could possibly remain in remission, fail again but enter into a second remission or die of breast cancer or other causes. Patients in second remission would then remain in that health state or die of breast cancer or other causes.
Summary of Data Used in Model
Although there have been several retrospective series that have examined the efficacy of adding an electron-beam boost to tangential radiation therapy,13-16 only a single randomized trial has been published to date that has directly addressed this issue.17 In that study from Lyon, France, 1,024 patients with breast tumors less than or equal to 3 cm in diameter all underwent local excision until "free" margins were achieved, then underwent axillary dissection and tangential radiation therapy to the entire breast (50 Gy in 20 2.5 Gy fractions over 5 weeks), and were then randomized to either no further local treatment or an electron-beam boost of 10 Gy. With a median follow-up period of 3.3 years, the authors reported that the addition of the boost resulted in a 20% reduction in the rate of local recurrence at 5 years (4.5% without the boost v 3.6% with it) and that it had no impact on overall survival. Therefore, in the baseline model, we assumed that the addition of the boost would reduce the rate of local recurrence by 20% but that it would have no impact on either the likelihood of developing metastatic disease or survival (Table 1). Because we assumed that there was no impact on survival by adding the boost, the rate of metastatic disease used in the baseline model for both strategies was based on data from the NSABP B-06 trial. We also assumed that the likelihood of developing metastatic disease was independent of the whether or not patients developed a local recurrence. Quality of life. Quality of life was incorporated into the analysis through the use of utilities. The utilities used in the baseline model were gathered from 97 actual breast cancer patients as part of a previous study and were measured using the standard gamble technique.6 Of the five health states for which utilities were measured, two are relevant for the purpose of this study. One health state involved treatment with conservative surgery and radiation therapy (including an electron-beam boost) and no local or distant recurrence but had a 10% risk of a local recurrence. Given that the addition of the boost results in a 2% absolute reduction in the risk of a local recurrence (eg, a 20% reduction of a 10% risk decreases the absolute risk of a local recurrence by 2%) and that this small benefit might be offset somewhat by the inconvenience (ie, 8 additional days of treatment) and potential acute and late toxicity of the boost, we assumed in the baseline model that the utilities for the two recurrence-free health states would be the same whether or not patients received the electron-beam boost. As part of the same study, patients’ utilities were also measured for a health state that involved treatment with conservative surgery and radiation therapy (again including the boost) followed by a local recurrence treated with a mastectomy and reconstructive surgery salvage regimen. In the baseline model, we again assumed that the utilities for the two locally recurrent health states would be the same whether or not patients received the boost. The mean values of the utilities for these health states were used in the baseline model (Table 1). Because it was assumed that the addition of the boost had no impact on the rate of distant metastasis and because cost-effectiveness analyses are incremental analyses (ie, only differences in outcomes and cost between the two strategies influence the results), the utilities for the metastatic health states have no impact on the cost-effectiveness ratio. Therefore, expert judgment was used to estimate their values. Costs. Direct medical, time, and transportation costs were included in our estimation of the incremental costs associated with the boost (Table 1). Direct medical costs included both facility and professional costs. Facility costs were estimated by multiplying the Medicare charges for the treatment planning, dosimetry, and administration of eight electron-beam boost treatments by the Medicare cost-to-charge ratio for radiation therapy at the Medical College of Virginia in 1995. We assumed that the boost was planned at the treatment unit without the use of an ultrasound or computed tomography scan and that a standard calculation was performed. Professional costs were estimated by multiplying the relative units of work associated with administering the boost, as estimated by Healthcare Consultants Inc by an estimate of the cost per unit of work ($8.00) on the basis of the California and Florida state medical associations’ physician payment scales.19 Time costs were estimated by multiplying an estimate of the number of hours the patient spent traveling to and undergoing another eight treatments by an estimate of the average hourly wage for women in their 60s ($9.40/h).20 Transportation costs were estimated by multiplying estimates of the miles traveled to undergo each additional treatment20 by the cost per mile ($0.31) plus the cost of parking ($2.00). Similar methods were used to estimate the costs associated with salvage mastectomy and reconstructive surgery. Discount rate. Future costs and benefits were discounted at a rate of 3% in the baseline model.
Cost-Effectiveness
Sensitivity Analyses
Because the cost-effectiveness analysis was found to be highly sensitive to the difference between the utility for treatment with a boost, no local recurrence and an 8% risk of a local recurrence, and no boost and a 10% risk of recurrence (see below), a Monte Carlo simulation was performed in which the values of these utilities were drawn repeatedly at random from their probability distributions and were then used in the model to recalculate the cost-effectiveness ratio.21,22 As mentioned above, we had, as part of a previous study, measured patients’ utilities for treatment with radiation therapy, no local recurrence and a 10% risk of a local recurrence (U10%), as well as for treatment without any radiation therapy, no local recurrence and a 40% risk of a local recurrence (U40%).6 Accordingly, the distribution of utilities associated with no local recurrence and a 10% risk of a local recurrence was readily available. Assuming a direct relationship between the change in patients’ utilities and the absolute difference in local recurrence rates, the distribution of the expected values of the utility for treatment with a boost, no local recurrence and an 8% risk of a local recurrence (U8%) was estimated for the entire data set (n = 96) using the following equation:
Baseline Analysis The Markov model estimated the cost of the boost and no-boost strategies to be $23,192 and $21,184, respectively (Table 2). Accordingly, the added cost associated with the boost strategy was $2,008, representing the added up-front cost of the boost less the downstream savings that resulted from the lower salvage costs associated with its use. The Markov model also estimated the number of QALYs for the boost strategy to be 7.164, while that for the no-boost strategy was estimated to be 7.157 QALYs, a difference of just 0.0065 QALYs, or 2.4 quality-adjusted days. This difference represented the greater likelihood that members of the no-boost cohort would experience a local recurrence, with its associated decline in quality of life. The incremental cost-effectiveness ratio was then calculated by dividing the incremental cost of the boost ($2,008) by its incremental benefit (0.0065 QALYs), resulting in a ratio of $308,923/QALY.
Sensitivity Analysis In our first threshold analysis, we examined the impact of the relative reduction in the local recurrences with the addition of the boost and found that it would have to increase from its baseline rate of 20% to 63% (an increase of over 300%) for the cost-effectiveness ratio to fall to $50,000/QALY (Table 3). Given that the boost is unlikely to ever be this effective, even if with further follow-up it is found to be moderately more effective in preventing local recurrences, it is still unlikely to be considered cost-effective. In a second analysis, we varied the total cost of the boost itself and found that its cost would have to fall from its baseline of $2,400 down to $754, which would cover the cost of just two boost treatments, for the ratio to fall to $50,000/QALY (Table 3).
In the baseline model, we also assumed that the utility for treatment with the boost and no local recurrence was the same as that for treatment without it and no local recurrence, based on the relatively small absolute reduction in local recurrence with the boost (ie, 2%). Therefore, in the third threshold analysis, we increased the utility for treatment with the boost and no local recurrence and found the cost-effectiveness ratio to be highly sensitive to this assumption. In fact, the utility for this health state would only have to increase by 0.005 (from 0.92 to 0.925) for the cost-effectiveness ratio to drop from over $300,000 to under $50,000 per QALY (Table 3). Because the analysis was so sensitive to the value of this utility, we chose to investigate this issue further by performing a probabilistic sensitivity analysis using a Monte Carlo simulation. For this analysis, we assumed that patients do place significant value in a 2% absolute reduction in the local recurrence rate (ie, that patients’ utility for the boost and no recurrence health state would be greater than that for treatment without the boost). When the Monte Carlo simulation was run 10,000 times using utility values for the nonrecurrent health states chosen at random from their probability distributions in the Markov model, the mean value of the cost-effectiveness ratio was $70,859/QALY, with a 95% confidence interval ranging from $53,141 to $105,182/QALY. For the entire run, the cost-effectiveness ratio was less than $50,000/QALY just 0.85% of the time. The recent publication of two trials that demonstrated a survival advantage after the addition of radiation therapy in the postmastectomy setting has renewed interest in the hypothesis that an improvement in local control will eventually translate into an improvement in overall survival.23,24 Accordingly, we next examined what impact the expected survival advantage for the boost might have on the cost-effectiveness ratio. In the NSABP B-06 trial, the 25% absolute reduction in the rate of local recurrence with the addition of any radiation therapy appears to result in no more than a 3% overall survival advantage at 10 years.2 Assuming that the relationship between local recurrence and overall survival is linear, with just a 2% absolute reduction in the local recurrence rate with the addition of the boost, we estimated the expected absolute survival benefit of the boost to be only 0.24%. When we then incorporated this survival advantage into the model, the cost-effectiveness ratio fell to $109,538/QALY (Table 4).
In an attempt to bias the analysis against the boost in terms of quality of life, we chose to assume in our baseline model that patients who experienced a local recurrence would undergo reconstructive surgery with a transverse rectus abdominus myocutaneous flap after their salvage mastectomy. However, our decision to do so also resulted in a $24,000 increase in the cost of treating a local recurrence with a salvage regimen. We therefore reran the model, excluding the additional cost of the reconstructive surgery, and found that the ratio rose to $357,000/QALY (Table 4). Lastly, the discount rate used in the baseline model was 3%. When the rate was varied between 0% and 5%, the cost-effectiveness ratio did not vary appreciably (Table 4).
Using our baseline model, we estimated the cost-effectiveness ratio for the use of an electron-beam boost in patients with early-stage breast cancer treated with lumpectomy (with negative margins), axillary dissection, and tangential radiation therapy to be $308,923/QALY. This ratio is well above commonly cited thresholds for the cost-effectiveness of medical interventions, despite the fact that several parameters in the model were purposefully biased in favor of the boost. Although this result was insensitive to variations in assumptions about the efficacy or the cost of the boost, it was highly sensitive to our assumption that patients would not place significant value on the small absolute reduction in the risk of a local recurrence resulting from addition of the boost. Although several retrospective studies have suggested that the use of a boost is not necessary in patients with negative margins,15,16 the recently published randomized trial from Lyon provides new evidence that the addition of the boost in patients with negative margins results in a statistically significant reduction of the local recurrence rate.17 However, although the relative reduction is a noteworthy 20%, the absolute reduction in the local recurrence rate is only 0.9% at 5 years. Viewed from a slightly different perspective, over 100 patients would need to be treated with a boost to prevent just one local recurrence during the first 5 years of follow-up. Because of the large number of patients enrolled onto the trial, this study had the statistical power to detect small differences in the local recurrence rate with the addition of the boost. However, given that the absolute difference is relatively small, we were interested in investigating whether this benefit is sufficiently large to justify its modest cost. In a previous analysis, we examined the cost-effectiveness of adding radiation therapy using both tangential fields and an electron-beam boost after lumpectomy in patients with early-stage breast cancer who chose breast conservation and found the cost-effectiveness ratio to be approximately $28,000/QALY18 (Fig 2). Because the ratio was well below $50,000/QALY, the commonly cited threshold for cost-effective care, we concluded that the use of radiation therapy in this setting is cost-effective, compared with other accepted medical interventions. In contrast, when we focused specifically on the addition of the electron-beam boost to the tangents in patients with negative margins, we found the cost-effectiveness ratio to be over $300,000/QALY. Accordingly, if one accepts the $50,000/QALY threshold, we must conclude that adding an electron-beam boost in this setting does not appear to be cost-effective.
The conclusion that the addition of the boost does not meet standard criteria for cost-effectiveness was insensitive to wide variations in estimates of the effectiveness and cost of the procedure. In contrast, the analysis was highly sensitive to our assumption that patients’ utilities for the recurrence-free health states were the same whether or not patients received a boost. It is therefore important to examine whether the assumption that patients’ quality of life after treatment but before recurrence would not vary with an absolute reduction in the risk of a local recurrence of 2% was reasonable. Indirect support for this assumption can be found in the breast cancer quality-of-life literature. Several studies have measured patients’ fear of recurrence after treatment with mastectomy versus that after treatment with lumpectomy and radiation therapy.25-33 Although the results were not statistically significant, patients treated with lumpectomy and radiation therapy appear to be at a slightly higher risk of recurrence than patients treated with mastectomy alone (odds ratio, 1.04 ± 0.08).34 Therefore, one could hypothesize that the women who have undergone breast-conserving therapy would have a greater fear of recurrence than those undergoing mastectomy. However, in all of these studies, the fear of recurrence was actually either the same as or greater after mastectomy, suggesting that a small decrease in the risk of recurrence is not associated with a meaningful change in patients’ quality of life. Nonetheless, we conducted an additional analysis to determine how our conclusions might change if our assumption was wrong (ie, that patients do value a 2% reduction in the risk of a local recurrence). This was accomplished by performing a Monte Carlo simulation in which the cost-effectiveness ratio was calculated 10,000 times using the probability distribution for the expected value of the utility for treatment with the boost and no local recurrence, assuming a direct relationship between the change in patients’ utilities and the absolute local recurrence rates. Although the mean value of the cost-effectiveness ratio was significantly lower than $300,000/QALY, it was still greater than the commonly cited threshold of $50,000/QALY. In addition, for the entire run, the cost-effectiveness ratio was only less than $50,000/QALY less than 1% of the time. Most importantly, the 95% confidence interval of the cost-effectiveness ratio did not overlap $50,000/QALY, suggesting that even if patients do value a 2% reduction in the risk of a local recurrence, the resulting ratio is still statistically significantly greater than $50,000/QALY. There are a number of limitations of our analysis that should be noted. The estimates of the probabilities of local recurrence used in the baseline model were based on data from a relatively immature trial. When published, the Lyon trial had a median follow-up period of only 3.3 years, and with further follow-up, the differences seen between the rates could increase or decrease.17 However, this seems unlikely, given that the rate of local recurrence after treatment with radiation therapy has been relatively constant with longer follow-up periods in all of the randomized trials examining the impact of adding any radiation therapy after lumpectomy.1-5 Another randomized trial examining this issue has also been completed, but its results have not yet been reported. As part of the European Organization for Research and Treatment of Cancer 22881 trial, 2,657 patients with microscopically negative margins after whole-breast tangential radiation therapy were randomized to no further treatment, whereas 2,661 patients were randomized to either a 16-Gy external-beam (photons or electrons) boost or a 15-Gy interstitial boost (H. Bartelink, personal communication, August 1998). It is possible that the local recurrence rates with and without the boost in the larger European Organization for Research and Treatment of Cancer trial could differ significantly from those reported in the Lyon trial. However, as highlighted by our sensitivity analysis, the magnitude of this difference would have to be unexpectedly high (ie, a relative reduction of 63% v 20%) to reach the commonly cited threshold of $50,000/QALY. Second, it should be noted that we chose to truncate our analysis and calculate the cost-effectiveness ratio at 10 years, based on the fact that none of the efficacy data that we used to estimate the probabilities used in our model extended much beyond 10 years. Had we extended the analysis even further, additional assumptions would need to be made. However, if the local recurrence rates were to change significantly beyond 10 years, it is possible that this could also have an impact on the results of the analysis. Third, we chose in our baseline model to set the number of fractions for the boost at eight and to plan the boost clinically. However, as highlighted again by our sensitivity analysis, the number of fractions would have to fall to two for the boost to be considered cost-effective, and the use of so few fractions in routine clinical practice seems highly unlikely. In addition, if an ultrasound or computed tomography scan had been used to plan the boost, the costs associated with its use would have been even greater, and it would be considered even less cost-effective. Fourth, in examining the cost-effectiveness of adding a boost after tangential radiation therapy to the whole breast, we chose only to examine the cost-effectiveness of an electron-beam boost and not an interstitial boost. Although there are some data to suggest that an interstitial boost might be more effective than an external-beam boost,35,36 the use of interstitial implants is presently quite uncommon in the United States. Its use is also likely to be considerably more expensive than the use of an electron-beam boost, thereby driving the cost-effectiveness ratio even higher. Lastly, when estimating the utility associated with an 8% risk of a local recurrence for the Monte Carlo simulation, we assumed that the relationship between the absolute risk of a local recurrence and the difference in utility was linear. We concede that a more complex relationship may exist between the risk of recurrence and patients’ utilities for the relevant health states, especially when the absolute differences are so small. On the basis of the results of our cost-effectiveness analysis, should use of the electron-beam boost be reconsidered in patients who have early-stage breast cancer and who are receiving adjuvant radiation after lumpectomy? Assuming that half of the 150,000 women diagnosed each year in the United States with early-stage breast cancer undergo breast-conserving therapy and that at least three quarters of those patients have negative margins, dropping the boost would result in an annual savings of approximately $135 million. At this time, for patients with negative margins, the answer appears to be yes. Unless long-term results from randomized trials of the electron-beam boost demonstrate that the addition of the boost results in an unexpectedly large, late impact on the local recurrence rate, it is demonstrated that patients place a significant value on a very small absolute reduction in the risk of a local recurrence, or that techniques can be developed which radically reduce the cost of the boost, it does not appear that the benefits of the boost will be sufficiently large enough to justify its cost.
We thank Dr Allen Lichter for his encouragement and helpful comments during the preparation of this manuscript.
Dr Hayman is a recipient of a Clinical Research Training Grant for Junior Faculty from the American Cancer Society. Presented at the Thirty-Fourth Annual Meeting of the American Society of Clinical Oncology, Los Angeles, CA, May 16-19, 1998.
1. Clark RM, Whelan T, Levine M, et al: Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer: An update—Ontario Clinical Oncology Group. J Natl Cancer Inst 88:1659-1664, 1996
2.
Fisher B, Anderson S, Redmond CK, et al: Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer [comments]. N Engl J Med 333:1456-1461, 1995 3. Forrest AP, Stewart HJ, Everington D, et al: Randomised controlled trial of conservation therapy for breast cancer: 6-Year analysis of the Scottish trial—Scottish Cancer Trials Breast Group. Lancet 348:708-713, 1996[Medline]
4.
Liljegren G, Holmberg L, Adami HO, et al: Sector resection with or without postoperative radiotherapy for stage I breast cancer: Five-year results of a randomized trial—Uppsala-Orebro Breast Cancer Study Group. J Natl Cancer Inst 86:717-722, 1994
5.
Veronesi U, Luini A, Del Vecchio M, et al: Radiotherapy after breast-preserving surgery in women with localized cancer of the breast [comments]. N Engl J Med 328:1587-1591, 1993
6.
Hayman JA, Fairclough DL, Harris JR, et al: Patient preferences concerning the trade-off between the risks and benefits of routine radiation therapy after conservative surgery for early-stage breast cancer. J Clin Oncol 15:1252-1260, 1997 7. Markiewicz DA, Fox KR, Schultz DJ, et al: Concurrent chemotherapy and radiation for breast conservation treatment of early-stage breast cancer. Cancer J Sci Am 4:185-193, 1998[Medline] 8. Pierce L, Strawderman M, Douglas K, et al: Conservative surgery and radiotherapy for early-stage breast cancer using a lung density correction: The University of Michigan experience. Int J Radiat Oncol Biol Phys 39:921-928, 1997[Medline] 9. Gage I, Schnitt S, Nixon A, et al: Pathologic margin involvement and the risk of recurrence in patients treated with breast-conserving therapy. Cancer 78:1921-1928, 1996[Medline] 10. Pezner R, Luk K, Lipsett J: To boost or not to boost: Aye, there’s the rub! Int J Radiat Oncol Biol Phys 21:529-530, 1991[Medline] 11. Recht A, Harris J: To boost or not to boost, and how to do it. Int J Radiat Oncol Biol Phys 20:177-178, 1991[Medline] 12. Recht A: When is more better? Int J Radiat Oncol Biol Phys 27:749-751, 1993[Medline] 13. Clark R, Wilkinson R, Miceli P, et al: Breast cancer experiences with conservation therapy. Am J Clin Oncol 10:461-468, 1987[Medline] 14. Chu A, Cope O, Russo R, et al: Patterns of local-regional recurrence and results in Stages I and II breast cancer treated by irradiation following limited surgery. Am J Clin Oncol 7:221-229, 1984[Medline]
15.
Ryoo M, Kagan A, Wollin M, et al: Prognosis factors for recurrence and cosmesis in 393 patients after radiation therapy for early mammary carcinoma. Radiology 172:555-559, 1989 16. Pezner R, Lipsett J, Deasi K, et al: To boost or not to boost: Decreasing radiation therapy in conservative breast cancer treatment when "inked" tumor resection margins are pathologically free of cancer. Oncol Biol Phys 14:873-877, 1988
17.
Romestaing P, Lehingue Y, Carrie C, et al: Role of a 10-Gy boost in the conservative treatment of early breast cancer: Results of a randomized clinical trial in Lyon, France. J Clin Oncol 15:963-968, 1997 18. Hayman J, Hillner B, Harris J, et al: Cost-effectiveness of routine radiation therapy following conservation surgery for early-stage breast cancer. J Clin Oncol 16:1022-1029, 1998[Abstract] 19. Hillner BE, Bear HD, Fajardo LL: Estimating the cost-effectiveness of stereotaxic biopsy for nonpalpable breast abnormalities: A decision analysis model. Acad Radiol 3:351-30, 1996[Medline] 20. US Bureau of the Census: Current Population Reports: Money Income in the United States—1995 (with separate data on valuation of noncash benefits). Washington, DC, United States Government Printing Office, 1996, p 36 21. Doubilet P, Begg CB, Weinstein MC, et al: Probabilistic sensitivity analysis using Monte Carlo simulation: A practical approach. Med Decis Making 5:157-177, 1985 22. Sisk JE, Moskowitz AJ, Whang W, et al: Cost-effectiveness of vaccination against pneumococcal bacteremia among elderly people. JAMA 278:1333-1339, 1997[Abstract]
23.
Ragaz J, Jackson SM, Le N, et al: Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer [comments]. N Engl J Med 337:956-962, 1997
24.
Overgaard M, Hansen PS, Overgaard J, et al: Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy—Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med 337:949-955, 1997 25. Ganz PA, Schag CC, Polinsky ML, et al: Rehabilitation needs and breast cancer: The first month after primary therapy. Breast Cancer Res Treat 10:243-253, 1987[Medline] 26. Ashcroft JJ, Leinster SJ, Slade PD: Breast cancer-patient choice of treatment: Preliminary communication. J Roy Soc Med 78:43-46, 1985[Abstract] 27. Bartelink H, van Dam F, van Dongen J: Psychological effects of breast conserving therapy in comparison with radical mastectomy. Int J Radiat Oncol Biol Phys 11:381-385, 1985[Medline] 28. Beckmann J, Johansen L, Richardt C, et al: Psychological reactions in younger women operated on for breast cancer: Amputation versus resection of the breast with special reference to body-image, sexual identity and sexual function. Dan Med Bull 30:10-13, 1983 29. Curran D, van Dongen JP, Aaronson NK, et al: Quality of life of early-stage breast cancer patients treated with radical mastectomy or breast-conserving procedures: Results of EORTC Trial 10801—The European Organization for Research and Treatment of Cancer (EORTC), Breast Cancer Co-operative Group (BCCG). Cancer 34:307-314, 1998 30. de Haes JC, van Oostrom MA, Welvaart K: The effect of radical and conserving surgery on the quality of life of early breast cancer patients. Eur J Surg Cancer 12:337-342, 1986 31. Kemeny MM, Wellisch DK, Schain WS: Psychosocial outcome in a randomized surgical trial for treatment of primary breast cancer. Cancer 62:1231-1237, 1988[Medline] 32. Lasry JC, Margolese RG: Fear of recurrence, breast-conserving surgery, and the trade-off hypothesis. Cancer 69:2111-2115, 1992[Medline] 33. Schain W, Edwards BK, Gorrell CR, et al: Psychosocial and physical outcomes of primary breast cancer therapy: Mastectomy vs excisional biopsy and irradiation. Cancer Res Treat 3:377-382, 1983
34.
Anonymous: Effects of radiotherapy and surgery in early breast cancer: An overview of the randomized trials—Early Breast Cancer Trialists’ Collaborative Group. N Engl J Med 333:1444-1455, 1995 (published erratum appears in N Engl J Med 334:1003, 1996) 35. Fourquet A, Campana F, Mosseri V, et al: Iridium-192 versus cobalt-60 boost in 3-7 cm breast cancer treated by irradiation alone: Final results of a randomized trial. Radiother Oncol 34:114-120, 1995[Medline] 36. Touboul E, Belkacemi Y, Lefranc J-P, et al: Early breast cancer: Influence of type of boost (electrons vs iridium-192 implant) on local control and cosmesis after conservative surgery and radiation therapy. Radiother Oncol 34:105-113, 1995[Medline] Submitted September 16, 1998; accepted August 16, 1999. This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2000 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
TOP
ABSTRACT
INTRODUCTION
) Chance events; (
) decisions.
