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Findings from NSABP protocol no. B‐04‐comparison of radical mastectomy with alternative treatments for primary breast cancer. I. Radiation compliance and its relation to treatment outcome
Author(s) -
Fisher Bernard,
Montague Eleanor,
Redmond Carol,
Deutsch Melvin,
Brown George R.,
Zauber Ann,
Hanson William F.,
Wong Audrey
Publication year - 1980
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19800701)46:1<1::aid-cncr2820460102>3.0.co;2-3
Subject(s) - medicine , breast cancer , radiation therapy , randomized controlled trial , mastectomy , clinical trial , surgery , cancer , total mastectomy , breast conserving surgery , radiological weapon , incidence (geometry) , physics , optics
Between 1971 and 1974, 1,665 women with primary operable breast cancer were entered into a prospective randomized clinical trial (NSABP Protocol No. B‐04) in order to compare the worth of radical mastectomy with alternative treatments. Six‐hundred forty‐six of the women, 352 clinically nodenegative and 294 node‐positive, were randomized so that they were to have been treated with total mastectomy and postoperative radiation. Due to a meticulous comprehensive program of radiation monitoring involving close cooperation between the NSABP Headquarters, the NSABP Radiation Monitoring Committee, the Radiological Physics Center at M. D. Anderson Cancer Center and participating institutions, it has been possible to determine protocol compliance of the radiation administered and to correlate any variation of radiation employed with treatment outcome. At the onset of the study and prior to any evaluation of treatment results, the Radiation Monitoring Committee defined minor variations from the protocol which were acceptable and those variations which were more major and unacceptable. While it was found that 53% of the 543 evaluable patients had been treated by radiation having some degree of variation from the protocol, it was ascertained that 77% of the 2.172 irradiated fields of those patients (82% in clinically node‐negative and 71% in clinically node‐positive patients) received radiation per protocol. Only 6.7% of all sites were the recipients of a major (unacceptabel) variation in radiation. Analysis of data demonstrated that there was a remarkable similarity in the incidence and rate of treatment failure (TF) or mortality between patients having some radiation variation, regardless of its degree or extent and those who were treated with no protocol variation. Results were similar when comparisons were made taking into consideration either the degree (minor or major low) or the extent (one or more than one field) of the radiation variation. A substantial number of clinically positive axillary node patients received only the radiation to the axillary field intended for those with clinically negative nodes, i.e., they failed to receive the specified radiation boost. Despite that deviation, there was no difference in TF or survival from those receiving the prescribed treatment. Moreover, findings were not different when the axilla was the only site of radiation deviation or there were deviations to other fields as well. Of singular importance was an inability to associate the localregional location of a recurrence with a low‐dose radiation deviation at the site. Almost all recurrences in clinically node‐negative patients were at sites treated per protocol. In positive‐node patients, supraclavicular and chest wall recurrences occurred in patients having acceptable radiation to those sites and axillary recurrences were equivalent in patients treated with or without deviations at that site. The findings from these investigations are not presented in order to indicate that the quality and quantity of radiation may be unimportant. They have been obtained under careful monitoring and the variations are within a relatively narrow range. Consequently, more general extrapolations from these must be made with circumspection. The observations do suggest, however, that there is some acceptable leeway in the use of radiation, at least for treatment of the extent of disease present in patients in this study. Moreover, they refute any consideration that the failure to demonstrate a significant advantage following the use of postoperative radiation in Protocol No. B‐04 could be related to the variation and inadequacy of radiation employed in a proportion of the patients. They tend to substantiate the contention that factors other than the type of operative procedure employed or the precision of administration of radiation are important in determining the survival of women with breast cancer. Finally, the mechanism whereby the radiation employed was quality controlled serves as a model for the mandatory monitoring of all modalities of therapy in cooperative clinical trials. Such monitoring, by providing more credible dat, will favorably affect the management of cancer patients. Cancer 46:1–13, 1980.