The Influence of Margin Width on Local Control of Ductal Carcinoma in Situ of the Breast

Silverstein, Melvin J.; Lagios, Michael D.; Groshen, Susan; Waisman, James; Lewinsky, Bernard S.; Martino, Silvana; Gamagami, Parvis; Colburn, William J.

doi:10.1056/nejm199905133401902

Cited by 614 publications

(354 citation statements)

References 35 publications

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“…This may explain why the 4-year local recurrence rates in the non-entered patients treated with LE+RT are relatively high compared to the patients in the trial treated with LE+RT. It might also indicate the importance of a complete excision, even with the application of RT (Silverstein et al, 1999;Bijker et al, 2001). In contrast, the non-entered patients treated with local excision alone had more similar 4-years local recurrence free rates in comparison to those patients treated with local excision in the trial, suggesting that LE alone is employed in those non-entered patients who were considered to have a low risk for local recurrence.…”

Section: Discussionmentioning

confidence: 99%

Effects of patient selection on the applicability of results from a randomised clinical trial (EORTC 10853) investigating breast-conserving therapy for DCIS

et al. 2002

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Selection of patients for randomised clinical trials may have a large impact on the applicability of the study results to the general population presenting the same disorder. However, clinical characteristics and outcome data on non-entered patients are usually not available. The effects of patient selection for the EORTC 10853 trial investigating the role of radiotherapy in breast conserving therapy for ductal carcinoma in situ have been studied, in an analysis of all patients treated for ductal carcinoma in situ in five participating institutes. The reasons for not entering patients were evaluated and treatment results of the randomised patients were compared to those not entered. A total of 910 patients were treated for ductal carcinoma in situ. Of these, 477 (52%) were ineligible, with the size of the lesion being the main reason for ineligibility (30% of all ductal carcinoma in situ). Of the 433 eligible patients, 278 (64%) were randomised into the trial. The main reasons for non-entry of eligible patients were either physicians' preference for one of the treatment arms (26%) or patients' refusal (9%). These percentages showed significant variation among the institutes. At 4 years follow-up, those patients not entered in the trial and treated with local excision and radiotherapy, had higher local recurrence rates than the patients randomised in the trial and treated with the same approach, (17 vs 2%, P=0.03). The patients treated with local excision alone had equal local recurrence rates (11% in both groups). Selection of patients may explain the differences in outcome of the randomised patients, and those not-entered. Thus, the results of this trial may not be applicable to all patients with ductal carcinoma in situ.

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Section: Discussionmentioning

confidence: 99%

Effects of patient selection on the applicability of results from a randomised clinical trial (EORTC 10853) investigating breast-conserving therapy for DCIS

et al. 2002

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“…These are all based primarily on nuclear morphology and also, in some, on the presence or absence of necrosis or cell polarisation. The histological type, together with the lesion size, and, perhaps of most significance, the size of the margin of clearance have been found to be the best determinants of the risk of recurrence (Lagios et al, 1989;Poller and Ellis, 1995;Silverstein et al, 1996Silverstein et al, , 1999Bijker et al, 2001a;Douglas-Jones et al, 2002).…”

mentioning

confidence: 99%

Grade of recurrent in situ and invasive carcinoma following treatment of pure ductal carcinoma in situ of the breast

et al. 2004

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The grade of recurrent in situ and invasive carcinoma occurring after treatment of pure ductal carcinoma in situ (DCIS) has been compared with the grade of the original DCIS in 122 patients from four different centres (The Royal Marsden Hospitals, London and Sutton, 57 patients; Guy's Hospital, London, 19 patients; Nottingham City Hospital, 31 patients and The Royal Liverpool Hospital, 15 patients). The recurrent carcinoma was pure DCIS in 70 women (57%) and in 52 women (43%) invasive carcinoma was present, which was associated with an in situ element in 43. In all, 19 patients developed a second recurrence (pure DCIS in 11 and invasive with or without an in situ element in eight). The majority of invasive carcinomas followed high-grade DCIS. There was strong agreement between the grade of the original DCIS and that of the recurrent DCIS (k ¼ 0.679), which was the same in 95 of 113 patients (84%). The grade of the original DCIS showed only fair agreement with the grade of recurrent invasive carcinoma (k ¼ 0.241), although agreement was stronger with the pleomorphism score of the recurrent carcinoma (k ¼ 0.396). There was moderate agreement, in recurrent invasive lesions, between the grade of the DCIS and that of the associated invasive element (k ¼ 0.515). Other features that showed moderate or strong agreement between the original and recurrent DCIS were necrosis and periductal inflammation. The similarity between the histological findings of the original and subsequent DCIS is consistent with the concept that recurrent lesions represent regrowth of residual carcinoma. In addition, although agreement between the grade of the original DCIS and that of any subsequent invasive carcinoma was only fair, there is no suggestion that low-grade DCIS lesions progress to higher grade lesions or to the development of higher grade invasive carcinoma. This is in agreement with immunohistochemical and molecular data indicating that low-grade and high-grade mammary carcinomas are quite different lesions.

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“…This is the reason an adjuvant therapy was always added after surgery. A study by Silverstein et al21 had demonstrated that the likelihood of local recurrence in patients that were not treated with adjuvant radiotherapy decreased as tumor‐free surgical margin increased. Another study by Dunne et al demonstrated that a 2 mm margin was superior to a margin less than 2 mm, but there was no significant difference seen with a greater than 5 mm margin 22.…”

Section: Methodsmentioning

confidence: 99%

“…Also, a uniform cancer cell distribution seems unlikely given the clinical findings that the recurrence rate decreased with an increase in surgical margins and drastically declined at 2 mm margin 21, 22. In addition, a half‐Gaussian distribution is simple and it also follows the IB‐IORT dose fall‐off, therefore it is speculated that the cancer cell killing and normal tissue sparing would benefit from the IB‐IORT dose fall off with this pattern, since the region with the largest cancer cell burden will get the largest dose for intensive killing.…”

Section: Methodsmentioning

confidence: 99%

Therapeutic analysis of Intrabeam‐based intraoperative radiation therapy in the treatment of unicentric breast cancer lesions utilizing a spherical target volume model

Schwid

Donnelly

Zhang

2017

J Applied Clin Med Phys

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It is postulated that the outcomes in treating breast cancer with intraoperative radiotherapy (IORT) would be affected by the residual cancer cell distribution within the tumor bed. The three‐dimensional (3D) radiation doses of IntrabeamTM (IB) IORT with a 4‐cm spherical applicator at the energy of 50 and 40 kV were calculated. The modified linear quadratic model (MLQ) was used to estimate the radiobiological responses of the cancer cells and interspersed normal tissues with various radiosensitivities. By comparing the average survival fraction of normal tissues in IB‐IORT and uniform dose treatment for the same level of cancer cell killing, the therapeutic ratios (TRs) were derived. The equivalent uniform dose (EUD) was found to increase with the prescription dose and decrease with the cancer cell infiltrating distance. For 50 kV beam at the 20 Gy prescription dose, the EUDs are 18.03, 16.49 and 13.56, 11. 29, and 9.28 Gy respectively, for 1.5, 3.0, 6.0, 9, and 15.0 mm of the cancer cell infiltrating distance into surrounding tissue. The dose rate of 50 kV is at least 1.87× higher than that of 40 kV beam. The EUDs of 50 kV beam are up to 15% higher than that of the 40 kV beam. The TR increases with the prescription dose, but decreases with the distance of cancer cell infiltration distance. Average TRs of 50 kV beam are up to 30% larger than that of 40 kV beam. In conclusion, IB‐IORT can provide a possible therapeutic advantage on sparing more normal tissue compared with the External Beam IORT (EB‐IORT) for shallowly populated unicentric breast lesion. Our data suggest that IB‐IORT dose size should be adjusted based on the individual patient's cancer cell infiltrating distance for delivering an effective dose, one dose‐fits‐all regimen may have undertreated some patients with large cancer infiltrating distance.

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The Influence of Margin Width on Local Control of Ductal Carcinoma in Situ of the Breast

Abstract: Postoperative radiation therapy did not lower the recurrence rate among patients with ductal carcinoma in situ that was excised with margins of 10 mm or more. Patients in whom the margin width is less than 1 mm can benefit from postoperative radiation therapy.

Cited by 614 publications

References 35 publications

Effects of patient selection on the applicability of results from a randomised clinical trial (EORTC 10853) investigating breast-conserving therapy for DCIS

Effects of patient selection on the applicability of results from a randomised clinical trial (EORTC 10853) investigating breast-conserving therapy for DCIS

Grade of recurrent in situ and invasive carcinoma following treatment of pure ductal carcinoma in situ of the breast

Therapeutic analysis of Intrabeam‐based intraoperative radiation therapy in the treatment of unicentric breast cancer lesions utilizing a spherical target volume model

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