Outcome at 8 years after breast-conserving surgery and radiation therapy for invasive breast cancer: influence of margin status and systemic therapy on local recurrence.

PURPOSE: To examine the relationship between pathologic margin status and outcome at 8 years after breast-conserving surgery and radiation therapy. PATIENTS AND METHODS: The study population comprised 533 patients with International Union Against Cancer/American Joint Committee on Cancer clinical stage I or II breast cancer who had assessable margins, who received at least 60 Gy to the primary tumor bed, and who had more than 8 years of potential follow-up. Each margin was scored (according to the presence of invasive or in situ disease that touched the inked surgical margin) as one of the following: negative, close, focally positive, or extensively positive. Outcome at 8 years was calculated using crude rates of first site of failure. A polychotomous logistic regression analysis was performed. Median follow-up time was 127 months. RESULTS: At 8 years, patients with close margins and those with negative margins both had a rate of local recurrence (LR) of 7%. Patients with extensively positive margins had an LR rate of 27%, whereas patients with focally positive margins had an intermediate rate of LR of 14%. In the polychotomous logistic regression model, margin status and the use of systemic therapy were the only two variables that had significant effects on the risk ratio of LR to remaining alive and free of disease. Among the 45 patients with focally positive margins who received systemic therapy, the crude LR rate was 7% at 8 years (95% confidence interval, 1% to 20%). CONCLUSION: Pathologic margin status and the use of adjuvant systemic therapy are the most important factors associated with LR among patients treated with breast-conserving surgery and radiation therapy.     

Clinical significance of margin status in postoperative radiotherapy for extremity and truncal soft-tissue sarcoma

PURPOSE: To evaluate whether adjuvant radiotherapy (RT) in extremity and truncal soft-tissue sarcoma (STS) patients with microscopically positive or close margins after excision can achieve comparable local control to that of excision with negative margin plus RT. METHODS AND MATERIALS: A total of 150 patients (111 extremity and 39 trunk cases) treated with conserving surgery and adjuvant RT was analyzed. All surgical margins were classified as being a negative margin or a positive or close margin based on pathologic margin width. RT was delivered with a shrinking-field technique in 150 patients (median, 63 Gy). RESULTS: All patients were divided into two groups: (A) excision with negative margins plus RT (n = 56) and (B) excision with positive or close margins plus RT (n = 94). Overall, the 5-year local failure-free survival in all patients was 72.9%, and no significant differences were found between the two groups (Group A, 74.7%; Group B, 71.6%). High tumor grade was found to be a significant predictor of local failure. However, Group A was superior to Group B in distant metastasis-free survival (p = 0.02). No significant differences were shown in overall survival between the two groups. CONCLUSIONS: In our series, margin status did not predict for LF when adjuvant RT was used. We believe that when adjuvant RT is used, re-resection may not be necessary for selected patients with positive or close pathologic margins in the management of extremity and truncal STS patients.     

Breast-conserving therapy for ductal carcinoma in situ of the breast: the French Cancer Centers' experience

PURPOSE: To assess the long-term outcome for women with ductal carcinoma in situ of the breast treated in current clinical practice by conservative surgery with or without definitive breast irradiation. METHODS AND MATERIALS: We analyzed 705 cases of ductal carcinoma in situ treated between 1985 and 1995 in nine French regional cancer centers; 515 underwent conservative surgery and radiotherapy (CS+RT) and 190 CS alone. The median follow-up was 7 years. RESULTS: The 7-year crude local recurrence (LR) rate was 12.6% (95% confidence interval [CI] 9.4-15.8) and 32.4% (95% CI 25-39.7) for the CS+RT and CS groups, respectively (p <0.0001). The respective 10-year results were 18.2% (95% CI 13.3-23) and 43.8% (95% CI 30-57.7). A total of 125 LRs occurred, 66 and 59 in the CS+RT and CS groups, respectively. Invasive or microinvasive LRs occurred in 60.6% and 52% of the cases in the same respective groups. The median time to LR development was 55 and 41 months. Nine (1.7%) and 6 (3.1%) nodal recurrences occurred in the CS+RT and CS groups, respectively. Distant metastases occurred in 1.4% and 3% of the respective groups. Patient age and excision quality (final margin status) were both significantly associated with LR risk in the CS+RT group: the LR rate was 29%, 13%, and 8% among women aged < or =40, 41-60, and > or =61 years (p <0.001). Even in the case of complete excision, we observed a 24% rate of LR (6 of 25) in women <40 years. Patients with negative, positive, or uncertain margins had a 7-year crude LR rate of 9.7%, 25.2%, and 12.2%, respectively (p = 0.008). RT reduced the LR rate in all subgroups, especially in those with comedocarcinoma (17% vs. 59% in the CS+RT and CS groups, respectively, p <0.0001) and mixed cribriform/papillary tumors (9% vs. 31%, p <0.0001). In the multivariate Cox regression model, young age and positive margins remained significant in the CS+RT group (p = 0.00012 and p = 0.016). Finally, the relative LR risk in the CS+RT group compared with the CS group was 0.35 (95% CI 0.25-0.51, p = 0.0001). Subsequent contralateral breast cancer occurred in 7.1% and 7.5% of the patients in the CS+RT and CS groups, respectively. CONCLUSION: Despite the absence of randomization, our results are extremely consistent with the updated National Surgical Adjuvant Breast Project B17 and European Organization for Research and Treatment of Cancer 10853 trials. We also noted that the LR risk was very high in women <40 years and/or in the case of incomplete excision.     

Factors associated with local recurrence and cause-specific survival in patients with ductal carcinoma in situ of the breast treated with breast-conserving therapy or mastectomy

PURPOSE: We reviewed our institution's experience treating patients with ductal carcinoma in situ (DCIS) of the breast to determine risk factors for ipsilateral breast tumor recurrence (IBTR) and cause-specific survival (CSS) after breast-conserving therapy (BCT) or mastectomy. MATERIALS AND METHODS: Between 1981 and 1999, 410 cases of DCIS (405 patients) were treated at our institution; 367 were managed with breast-conserving surgery (54 with lumpectomy alone and 313 with adjuvant radiation therapy (RT) [median dose, 45 Gy]). Of these 313 patients, 298 received also a supplemental boost of RT to the lumpectomy cavity (median dose, 16 Gy). Forty-three patients underwent mastectomy; 2 (5%) received adjuvant RT to the chest wall. A true recurrence/marginal miss (TR/MM) IBTR was defined as failure within or adjacent to the tumor bed in patients undergoing BCT. Median follow-up for all patients was 7 years (mean: 6.1 years). RESULTS: Thirty patients (8.2%) experienced an IBTR after BCT (25 [8%] after RT, 5 [9.3%] after no RT), and 2 patients (4.7%) developed a chest wall recurrence after mastectomy. Of the 32 local failures, 20 (63%) were invasive (18/30 [60%] after BCT and 2/2 [100%] after mastectomy), and 37% were DCIS alone. Twenty-four (80%) of the IBTRs were classified as TR/MM. The 10-year freedom from local failure, CSS, and overall survival after BCT or mastectomy were 89% vs. 90% (p = 0.4), 98% vs. 100% (p = 0.7), and 89% vs. 100% (p = 0.3), respectively. Factors associated with IBTR on Cox multivariate analysis were younger age (p = 0.02, hazard ratio [HR] 1.06 per year), electron boost energy < or = 9 MeV (p = 0.03, HR 1.41), final margins < or = 2 mm (p = 0.007; HR, 3.65), and no breast radiation (p = 0.002, HR 5.56). On Cox univariate analysis for BCT patients, IBTR, TR/MM failures, and predominant nuclear Grade 3 were associated with an increased risk of distant metastases and a reduced CSS. CONCLUSIONS: After treatment for DCIS, 10-year rates of local control, CSS, and overall survival were similar after mastectomy and BCT. Young age (<45 years), close/positive margins (< or = 2 mm), no breast radiation, and lower electron boost energies (< or = 9 MeV) were associated with IBTR. Local failure and predominant nuclear Grade 3 were found to have a small (4%-12%) but statistically significantly negative impact on the rates of distant metastasis and CSS. These results suggest that optimizing local therapy (surgery and radiation) is crucial to improve local control and CSS in patients treated with DCIS.     

Outcomes and factors impacting local recurrence of ductal carcinoma in situ

BACKGROUND: The optimal management of ductal carcinoma in situ (DCIS) remains controversial. Investigators have focused on identifying patients who are eligible for treatment by excision alone. A retrospective analysis of patients with DCIS treated by various modalities was conducted to compare outcomes and determine factors significant for local recurrence (LR). METHODS: Between 1985-1992, 88 consecutive diagnoses of DCIS were identified in 85 patients. Seventy-four percent were detected mammographically. The most common histologic subtypes were comedo (54%) and cribriform (23%). Tumor sizes were < 2.5 cm (49%), > 2.5-5 cm (26%), > 5 cm (23%), and unknown (2%). Final resection margins were tumor free (75%), close/positive (23%), and unknown (2%). Treatment methods included mastectomy (30%), localized surgery and radiation therapy (LSR) (43%), or wide localized surgery alone (LS) (27%). Radiation therapy (RT) was comprised of 50 grays to the breast, and 53% of treated patients received local "boost" irradiation. RESULTS: The median follow up was 8.3 years. The overall recurrence rate was 13. 6%, whereas the median time to LR was 27.8 months. Recurrence rates according to treatment modality were: LS: 25%; LSR: 13%; and mastectomy: 4%. However, if surgical margins were tumor free, LSR had a LR rate of 3.4%. After RT, no LR occurred prior to 15 months, and 4 of 5 tumors were noninvasive. Nine patients treated by excision alone conformed to the criteria of Lagios et al. criteria and LR occurred in three of nine tumors. Of the factors analyzed, margin status was found to be the best predictor for LR (P = 0.05). CONCLUSIONS: If surgical margins are tumor free, the LSR regimen is equivalent to mastectomy for local tumor control. Annual mammograms may be adequate for the follow-up of patients with irradiated breasts, but biannual studies still are recommended for patients treated with excision alone.     

Negative margin status improves local control in conservatively managed breast cancer patients

OBJECTIVE: The purpose of this study was to determine the impact of final pathologic margin status on breast relapse-free survival, distant metastasis-free survival, and overall survival in patients undergoing conservative surgery and radiation therapy for invasive breast cancer. MATERIALS AND METHODS: Between January 1970 and December 1990, 984 patients underwent conservative surgery and radiation therapy at our institution as treatment for invasive breast cancer. After lumpectomy, patients were given radiation therapy to the intact breast with or without treatment to regional nodes with the routine use of electron boost to a total median tumor bed dose of 64 Gy. Pathology reports were available for review in 871 patients. Re-excision was carried out in 294 of these patients. For this analysis, patients were divided into four groups based on final pathologic margin status: negative (n = 278), dose (typically within 2 mm, n = 47), positive (n = 55), or indeterminate (n = 491). RESULTS: There were no significant differences between the groups with respect to age, histology, estrogen and progesterone receptor status, tumor location, or total radiation dose. Patients with negative margins were more likely than those with positive margins to have T1 mammographically detected lesions, to have negative nodal status, and to have undergone re-excision. Patients with positive margins were more likely to receive adjuvant chemotherapy or hormone therapy (P = 0.001). As of July 1998, with a median follow-up of 13 years, the median breast relapse-free survival, distant metastasis-free survival, and overall survival rates at 10 years for the entire cohort of patients were 86%, 81%, and 76%, respectively. Breast relapse-free survival at 10 years was 98% for patients with negative margins versus 98% for those with close margins versus 83% for those with positive margins versus 82% for those with indeterminate margins. There were no significant differences in breast relapse-free survival between patients with negative and dose margins or between patients with positive and indeterminate margins. Although the negative margin status also conferred an overall survival and distant metastasis-free survival advantage, this difference is confounded by the earlier stage of disease in these patients, and margin status did not influence overall survival in multivariate analysis. CONCLUSION: In patients undergoing conservative management of breast cancer, negative margin status significantly improves breast relapse-free survival. Close margins appear equivalent to negative margins, and indeterminate margins appear equivalent to positive margins. Adjuvant chemotherapy or hormone therapy did not counteract the adverse impact of positive margin status. Re-excision to obtain dear surgical margins is recommended, even if a radiation boost or adjuvant systemic therapy is planned.     

Prognosis after local recurrence after conservative surgery and radiation for early-stage breast cancer

PURPOSE: To determine the long-term prognosis of patients who develop a local recurrence (LR) after conservative surgery (CS) and radiation therapy (RT) for early-stage invasive breast cancer. METHODS AND MATERIALS: Between 1970 and 1987, 2102 patients with clinical Stage I-II breast cancer were treated with CS+RT. LR was defined as any recurrence within the ipsilateral breast with or without simultaneous regional nodal or distant metastasis. Patients were at risk for a LR until the first of distant metastases, second nonbreast malignancy, or death (DF/S/D). The final study population comprised 341 patients with LR. The median time to LR was 72 months. The median follow-up time after LR was 85 months. A proportional hazards model of time from LR to DF/S/D was done to investigate the influence of factors at initial diagnosis and at LR on subsequent outcome. RESULTS: The actuarial freedom from DF/S/D 5 years after LR was 65% and the survival was 81%. Variables significantly associated with time to DF/S/D were: LR histology (invasive vs. ductal carcinoma in situ, hazard ratio [HR] = 4.1, p < 0.0001); local therapy for LR (none vs. mastectomy or unknown, HR = 3.2, p < 0.0001; and CS +/- RT vs. mastectomy or unknown, HR = 2.0, p = 0.02); time to LR (< or =2 years vs. >5 years, HR = 2.6, p < 0.0001; and 2-5 years vs. >5 years, HR = 1.8, p = 0.006); and age at initial diagnosis (> or =60 vs. <60, HR = 1.6, p = 0.01). CONCLUSIONS: Many patients with LR after CS+RT have prolonged distant disease-free survival, particularly those able to be treated with mastectomy. Patients with a noninvasive LR, longer interval to LR, or age <60 had a longer time to distant failure, second malignancy, or death than other patients.     

Do surgical margins matter after mastectomy? A systematic review

BackgroundNo consensus exists regarding adequacy of margins after mastectomy.To determine if pathological margin proximity is associated with local (LR) or distant recurrence after mastectomy for early invasive breast cancer or ductal carcinoma in situ.MethodsA systematic review of literature published from 1980 to 2019 and meta-analysis was conducted. Unpublished data were sought from authors (PROSPERO (CRD42019127541)).Thirty-four studies comprising 34,833 breast cancer patients were included in the quantitative synthesis. Eligible studies reported on patients undergoing curative mastectomy for cancer allowing estimation of outcomes in relation to margin status/width.The association between pathological margin status and local (LR) and distant recurrence was considered using random effects modelling. PRISMA guidelines were followed.ResultsPositive margins were associated with increased LR on multivariable analyses (HR, 2·64, (95%CI 2·01–3·46)) and LR was higher regardless of the distance of tumour from the margin defined as positive. After skin-sparing mastectomy, positive margins were associated with increased LR (HR 3·40, (95%CI 1·9–6·2)). In the 4 studies reporting distant recurrence, patients with involved margins had a higher risk (HR 1·53, (95%CI 1·03–2·25)).ConclusionsFailure to achieve clear margins after mastectomy may increase the risks of local and distant recurrence. Adequate margin clearance should be recommended to minimize recurrence after mastectomy in National and International Guidelines.     

Quality of surgery and neoadjuvant combined therapy in the ISG-GEIS trial on soft tissue sarcomas of limbs and trunk wall

BackgroundTo explore correlation between the quality of surgery and outcome in high-risk soft tissue sarcoma (STS) patients treated within a phase III randomized trial.Patients and MethodsIn the trial, all patients received three cycles of preoperative chemotherapy (CT) with epirubicin 120 mg/m² and ifosfamide 9 g/m² and were randomly assigned to receive two further postoperative cycles. Radiotherapy (RT) could be delivered in the preoperative or postoperative setting. The association between surgical margins and overall survival (OS) was studied in a univariate and multivariate fashion.ResultsTwo hundred and fifty-two patients completed the whole treatment and were operated conservatively. At a median follow-up of 60 months (IQR, 45–74 months), the 5-year OS was 0.73, even in patients with positive and negative margins. The 5-year cumulative incidence (CI) of local recurrence (LR) in patients with positive and negative microscopic margins was 0.17 (standard error, SE, 0.08) and 0.03 (SE, 0.01), respectively. In the subgroup of patients receiving combined preoperative CT–RT and with positive surgical margins, the CI of LR was 0.ConclusionsIn this setting of high-risk STS treated by preoperative CT or CT–RT, the negative impact of positive margins on the outcome was limited. When close margins can be anticipated preoperative CT–RT may be a reasonable option to maximize the chance of cure.     

Is dose de-escalation possible in sarcoma patients treated with enlarged limb sparing resection?

PurposeTo evaluate the impact of dose de-escalation in a large series of resected limbs soft tissue sarcomas (STS).MethodsData were retrospectively analysed from 414 consecutive patients treated for limb STS by enlarged surgery and radiotherapy at Gustave Roussy from 05/1993 to 05/2012. Radiotherapy (RT) dose level was decided by the multidisciplinary staff and depended upon the quality of surgery and margins size.ResultsRT was delivered prior (13%) or after (87%) surgery. Seven patients (2%) had pre- and a postoperative RT boost. Median delivered RT dose was 50 Gy (36–70 Gy), and 33% received ≥55 Gy. At a median follow-up of 6.8 years, the 5-year actuarial local relapse (LR) rate was 7% (95% CI: 4.4–10%). The median time to the first LR was 2.7 years (range: 0.6–11.2 years). The LR was most often located within the irradiated field (26/32; 81%), where the median total applied dose was 56 Gy (range, 40–60 Gy). The 5-year LR rates were 4%, and 15% in patients receiving <55 Gy, and in those who had ≥55 Gy (p < 0.001), respectively. In the multivariate analysis, dose ≥55 Gy (HR [hazard ratio]: 2.9; p = 0.02), certain histological subtypes (HR: 7.8; p < 0.001), and minimal surgical margins <1 mm (HR: 2.9; p = 0.02) were associated to higher LR rates. In the subgroup of patients with “positive” margins <1 mm (n = 102), these histological subtypes (HR: 4.4; p = 0.03), and inadequate initial surgery justifying re-excision (HR: 3; p = 0.048) predicted for an increased LR, whereas dose of irradiation did not (p = 0.2). Patients who had late complications (n = 64; 15%) received higher doses of irradiation as compared with other patients (median: 55 Gy vs. 50 Gy, respectively; p < 0.001).ConclusionIn this retrospective analysis of patients having enlarged surgery and RT, histological subtype is the strongest predictor of LR, whereas dose de-escalation did not lead to worse outcomes. A dose of 50 Gy may be recommended in case of planned enlarged surgery with R0 margins.     

The value of a positive margin for invasive carcinoma in breast-conservative treatment in relation to local recurrence is limited to young women only

PURPOSE: To identify the importance of positive margins for invasive carcinoma on local control in patients treated with breast-conservative treatment (BCT). METHODS AND MATERIALS: A total of 1752 BCT with known margins were analyzed. Fifty-five patients had a second BCT, leaving 1697 patients for analysis. The margins were positive in 193/1752 BCT (11%). The median follow-up was 78 months. RESULTS: The 5- and 10-year local recurrence rates (LRR) were 3.1% and 6.9%, respectively, for negative margins vs. 5.6% and 12.2% for positive margins. A statistical interaction between age category and margin status was noted in relation to disease-free survival (DFS) and local relapse-free survival. The 5-year LRR for women < or =40 years was 8.4% for negative margins and 36.9% for positive margins (p = 0.005). In a multivariate analysis, a positive margin was significant. The 5-year LRR for women >40 years was 2.6% for negative and 2.2% for positive margins. The 5-year DFS for women 40 years was 84.3% for positive and 87.2% for negative margins. CONCLUSION: Women < or =40 years are a special category of patients in breast cancer. Women < or =40 years must have negative margins for invasive carcinoma when treated with BCT. Minimum surgery for an optimal cosmetic result followed by irradiation, even with microscopic positive margins for invasive carcinoma, yields excellent results with regard to local control in patients older than 40 years.     

Long-term outcomes after function-sparing surgery without radiotherapy for soft tissue sarcoma of the extremities and trunk.

PURPOSE: To define the rate of local recurrence (LR) and identify prognostic factors for LR for patients with soft tissue sarcoma (STS) treated with function-sparing surgery (FSS) without radiotherapy (RT). PATIENTS AND METHODS: Between 1970 and 1994, 242 patients with STS of the trunk and extremity presented with primary localized disease, 74 of whom were treated with FSS without RT (31%). The median tumor size was 4 cm (range, 0.5 to 31 cm). There were 40 patients with grade 1 tumors and 34 with grade 2 and 3 tumors. Median follow-up was 126 months. RESULTS: The 10-year actuarial local control rate was 93% +/- 4%. Resection margin status was a significant predictor for LR. Patients with closest histologic resection margins of less than 1 cm had a 10-year local control rate of 87% +/- 6% compared with 100% for patients with closest histologic resection margins of >/= 1 cm (P =.04). There was no significant association between LR and tumor grade, size, site (truncal v extremity), or depth (superficial v deep). For all patients, the 10-year actuarial survival rate was 73% +/- 6%. CONCLUSION: The 7% LR rate after treatment of STS with FSS without RT reported herein is comparable to published rates following treatment where adjuvant RT is used. These results suggest there may be a select subset of patients with STS in whom carefully performed FSS may serve as definitive therapy and in whom adjuvant RT may not be necessary. However, further study is needed to carefully define this subset of patients and to identify the optimal surgical approach and technique for patients treated without RT.     

Effect of margins on ipsilateral breast tumor recurrence after breast conservation therapy for lymph node-negative breast carcinoma

BACKGROUND: Breast conservative surgery (CS) with radiotherapy (RT) is the most commonly used treatment for early-stage breast carcinoma. However, there is controversy regarding the importance of the pathologic margin status on the risk of ipsilateral breast tumor recurrence (IBTR). The current study evaluated the effect of the pathologic margin status on IBTR rates in a cohort of women with lymph node-negative breast carcinoma treated with CS and RT. METHODS: Between August 1980 and December 1994, 452 women with pathologically lymph node-negative breast carcinoma were treated with CS and RT at Westmead Hospital (Westmead, Australia). Central pathology review was performed for all women. The final margins were negative for 352 women (77.9%), positive (invasive and/or in situ) for 42 women (9.3%), and indeterminate for 58 women (12.8%). Information regarding an extensive intraductal component (EIC), lymphovascular invasion, pathologic tumor size, histologic grade, and nuclear grade was available for most women. After macroscopic total excision of the tumor, all women received whole-breast irradiation (usually 45-50.4 grays [Gy]) and the majority of women also received a local tumor bed boost (range, 8-30 Gy). RESULTS: After a median follow-up of 80 months, 34 women (7.5%) developed an IBTR. The crude 5-year rates of IBTR for women with negative margins, positive margins, and indeterminate margins were 3.1%, 11.9%, and 6.9%, respectively. For women with negative margins, the 5-year and 10-year actuarial rates of freedom from IBTR were 96% and 92%, respectively, compared with 88% and 75%, respectively, for women with positive margins (P = 0.003). Univariate analysis demonstrated that the only factors associated with a significantly higher risk of IBTR were age at diagnosis (P < 0.050) and margin status (P = 0.005). Multivariate analysis showed that both age and margin status were independent predictors of IBTR. None of 24 patients with an EIC and negative margins were found to have developed an IBTR. CONCLUSIONS: The results of the current study were comparable to other published reports and supported the association of higher IBTR rates with positive or indeterminate margins compared with negative, pathologic margins. Furthermore, young age (age < 35 years at diagnosis) was associated with the highest risk of IBTR regardless of margin status.     

Margin status and the risk of local recurrence in patients with early-stage breast cancer treated with breast-conserving therapy

We sought to assess whether a close surgical margin (>0 and <2 mm) after breast-conserving therapy (BCT) confers an increased risk of local recurrence (LR) compared with a widely negative margin (≥2 mm). We studied 906 women with early-stage invasive breast cancer treated with BCT between January 1998 and October 2006; 91 % received adjuvant systemic therapy. Margins were coded as: (1) widely negative (n = 729), (2) close (n = 85), or (3) close (n = 84)/positive (n = 8) but having no additional tissue to remove according to the surgeon. Cumulative incidence of LR and distant failure (DF) were calculated using the Kaplan–Meier method. Gray’s competing-risk regression assessed the effect of margin status on LR and Cox proportional hazards regression assessed the effect on DF, controlling for biologic subtype, age, and number of positive lymph nodes (LNs). Three hundred seventy-seven patients (41.6 %) underwent surgical re-excision, of which 63.5 % had no residual disease. With a median follow-up of 87.5 months, the 5-year cumulative incidence of LR was 2.5 %. The 5-year cumulative incidence of LR by margin status was 2.3 % (95 % CI 1.4–3.8 %) for widely negative, 0 % for close, and 6.4 % (95 % CI 2.7–14.6 %) for no additional tissue, p = 0.3. On multivariate analysis, margin status was not associated with LR; however, triple-negative subtype (AHR 3.7; 95 % CI 1.6–8.8; p = 0.003) and increasing number of positive LNs (AHR 1.6; 95 % CI 1.1–2.3; p = 0.025) were associated. In an era of routine adjuvant systemic therapy, close surgical margins and maximally resected close/positive margins were not associated with an increased risk of LR compared to widely negative margins. Additional studies are needed to confirm this finding.     

Extent of excision margin width required in breast conserving surgery for ductal carcinoma in situ

BACKGROUND: Breast conserving surgery (BCS) is common practice for unifocal ductal carcinoma in situ (DCIS) less than 4 cm in size, but the extent of tumor free margin width around DCIS necessary to minimize recurrence is unclear. METHODS: Clinical and pathologic details were recorded from all patients with pure DCIS < 4 cm in size, treated with BCS between 1978 and 1997. Histologic margins were measured by using an ocular micrometer. Patients with clear margins (> 1 mm) were divided up into 3 groups for analysis based on margin of normal tissue excised: 1.1-5 mm, 5.1-10 mm, and 10.1-40 mm. RESULTS: There were 66 patients with close margins (< or = 1 mm), of which 25 cases (37.9%) recurred. The recurrence rates for the 3 clear margin groups ranged from 4.5-7.1%. Median followup was 47 months (range 12-197 mos). Risk of recurrence in the group with close margins was greater than the subgroups with clear margins (P < 0.001); no differences in recurrence was seen between the individual subgroups with clear margins. Nuclear Grade 3 was predictive of recurrence (P = 0.03). Following excision alone, the recurrence rate was 18.6%, compared with 11.1% when radiotherapy was given as adjuvant therapy. Women with clear margins following excision had a recurrence rate of only 8.1%. CONCLUSION: After BCS for DCIS, close margins were associated with a high risk of local recurrence. Radiotherapy did not compensate for inadequate surgical clearance.     

The significance of the pathology margins of the tumor excision on the outcome of patients treated with definitive irradiation for early stage breast cancer.

To evaluate the significance of the pathology margins of the tumor excision on the outcome of treatment, an analysis was performed of 697 consecutive women with clinical Stage I or II invasive carcinoma of the breast treated with breast-conserving surgery and definitive irradiation. Complete gross excision of the primary tumor was performed in all cases, and an axillary staging procedure was performed to determine pathologic axillary lymph node status. The 697 patients were divided into four groups based on the final pathology margin from the primary tumor excision or from the re-excision if performed. These four groups were: (a) 257 patients with a negative margin (greater than 2 mm), (b) 57 patients with a positive margin, (c) 37 patients with a close margin (less than or equal to 2 mm), and (d) 346 patients with an unknown margin. The patients with positive final pathology margins were focally positive on microscopic examination. Patients with grossly positive margins or with diffusely positive microscopic margins were treated with conversion to mastectomy. There was a significant difference in the total radiation dose for the four groups (median dose of 6000 vs 6500 vs 6400 vs 6240 cGy, respectively; p less than .0001). There was no significant difference among the four groups for 5-year actuarial overall survival (p = .19), no evidence of disease (NED) survival (p = .95), or relapse-free survival (p = .80). There was no significant difference among the four groups for five year actuarial local or regional control (all p greater than or equal to .29). Subset analyses did not identify any poor outcome subgroups. These results have demonstrated that selected patients with focally positive or close microscopic pathology margins can be adequately treated with definitive breast irradiation. Patient selection and the technical delivery of radiation treatment including a boost may have been important contributing factors to the good outcome in these patients.     

Effect of subcentimeter nonpositive resection margin on hepatic recurrence in patients undergoing hepatectomy for colorectal liver metastases. Evidences from 663 liver resections.

OBJECTIVE: To elucidate if a nonpositive <1-cm resection margin has any effect on hepatic recurrence in patients undergoing liver resection for colorectal liver metastases. PATIENTS AND METHODS: Six hundred and nine patients underwent 663 liver resections. Patients with positive margin were excluded from the analysis. Two groups were studied: group A, <1-cm resection margin and group B, > or =1-cm resection margin. RESULTS: A total of 545 liver resections in 523 patients were carried out with nonpositive resection margins. With a median follow-up of 25 months, the 5-year cumulative hepatic recurrence reached 54% in group A (n = 206) and 41% in group B (n = 339). Factors associated with hepatic recurrence were synchronic metastases (P = 0.0015), bilobar (P < 0.001), two or more metastases (P < 0.001), margin <1 cm (P = 0.0123) and extrahepatic disease (P = 0.0037). A strong correlation between resection margin and number of metastases was confirmed (P < 0.001). At multivariate analysis only two factors were independent predictors of hepatic recurrence: multinodular disease in the liver specimen [> or =4 metastases hazard ratio (HR) = 3.45; 95% confidence interval (CI): 2.2-5.38; P < 0.001] and extrahepatic disease at hepatectomy (HR = 1.58; 95% CI: 1.58-3.32). CONCLUSION: Subcentimeter nonpositive resection margins do not directly influence hepatic recurrence in patients undergoing hepatectomy for colorectal liver metastases.     

Long-term results of breast conserving surgery for stages I and II breast cancer: experiences at Osaka Medical Center for Cancer and Cardiovascular Diseases

PURPOSE: The purpose of this study is to summarize the long-term results of breast conserving surgery (BCS) for Japanese patients with stage I and II breast cancer at a single institute and to identify risk factors for local recurrence after BCS. PATIENTS AND METHODS: Between October 1986 and June 2000, 979 women underwent BCS with or without radiation therapy (RT). Overall survival, disease free survival and local recurrence rates were calculated by the Kaplan-Meier method. Risk factors for local recurrence were examined by multivariate analysis using the Cox proportional regression model. RESULTS: The 10-year overall survival rates were 90.9% for the surgery and radiation therapy (RT group) and 89.3% for the surgery only group with a median follow-up time of 46 months. The 10-year disease free survival rates were 85.1% in the RT group and 69.2% in the surgery only group (p=0.0001). The positive margin rate was 14.1% (138/979). The 10-year overall survival rate of the patients with positive margins was 87.9%, compared with 90.8% for patients with negative margins (N.S.). The cumulative incidence of local recurrence at 10 years was significantly lower in the RT group (7.2% ) than in the surgery only group (27.5% ) (p<0.0001). Multivariate analysis showed that positive margins and lack of post-operative irradiation or adjuvant endocrine therapy were risk factors for non-inflammatory local recurrence. CONCLUSIONS: Our study indicates that BCS can be performed for Japanese women with early breast cancer. The margin status and post-operative irradiation had no influence on overall survival while but were significantly related to local recurrence.     

Patients with early stage invasive cancer with close or positive margins treated with conservative surgery and radiation have an increased risk of breast recurrence that is delayed by adjuvant systemic therapy

Purpose: The association between a positive resection margin and the risk of ipsilateral breast tumor recurrence (IBTR) after conservative surgery and radiation is controversial. The width of the resection margin that minimizes the risk of IBTR is unknown. While adjuvant systemic therapy may decrease the risk of an IBTR in all patients, its impact on patients with positive or close margins is largely unknown. This study examines the interaction between margin status, margin width, and adjuvant systemic therapy on the 5- and 10-year risk of IBTR after conservative surgery and radiation.

Methods and Materials: A series of 1,262 patients with clinical Stage I or II breast cancer were treated by breast-conserving surgery, axillary node dissection, and radiation between March 1979 and December 1992. The median follow-up was 6.3 years (range 0.1–15.6). The median age was 55 years (range 24–89). Clinical size was T1 in 66% and T2 in 34%. Seventy-three percent of patients were node-negative. Only 5% of patients had tumors that were EIC-positive. Forty-one percent had a single excision, and 59% had a reexcision. The final margins were negative in 77%, positive in 12%, and close (≤ 2 mm) in 11%. The median total dose to the tumor bed was 60 Gy with negative margins, 64 Gy with close margins, and 66 Gy with positive margins. Chemotherapy ± tamoxifen was used in 28%, tamoxifen alone in 20%, and no adjuvant systemic therapy in 52%.

Results: The 5-year cumulative incidence (CI) of IBTR was not significantly different between patients with negative (4%), positive (5%), or close (7%) margins. However, by 10 years, a significant difference in IBTR became apparent (negative 7%, positive 12%, close 14%, p = 0.04). There was no significant difference in IBTR when a close or positive margin was involved by invasive tumor or DCIS. Reexcision diminished the IBTR rate to 7% at 10 years if the final margin was negative; however, the highest risk was observed in patients with persistently positive (13%) or close (21%) (p = 0.02) margins. The median interval to failure was 3.7 years after no adjuvant systemic therapy, 5.0 years after chemotherapy ± tamoxifen, and 6.7 years after tamoxifen alone. This delay to IBTR was observed in patients with close or positive margins, with little impact on the time to failure in patients with negative margins. The 5-year CI of IBTR in patients with close or positive margins was 1% with adjuvant systemic therapy and 13% with no adjuvant therapy. However, by 10 years, the CI of IBTR was similar (18% vs. 14%) due to more late failures in the patients who received adjuvant systemic therapy.

Conclusion: A negative margin (> 2 mm) identifies patients with a very low risk of IBTR (7% at 10 years) after conservative surgery and radiation. Patients with a close margin (≤ 2 mm) are at an equal or greater risk of IBTR as with a positive margin, especially following a reexcision. A margin involved by DCIS or invasive tumor has the same increased risk of IBTR. A reexcision of an initially close or positive margin that results in a negative final margin reduces the risk of IBTR to that of an initially negative margin. A close or positive margin is associated with an increased risk of IBTR even in patients who are EIC-negative or receiving higher boost doses of radiation. The median time to IBTR is delayed; however, the CI is not significantly decreased by adjuvant systemic therapy in patients with close or positive margins—the 5 year results in these patients underestimate their ultimate risk of recurrence.