Local Recurrence Rates are Low in High-Risk Neoadjuvant Breast Cancer in the I-SPY 1 Trial (CALGB 150007/150012; ACRIN 6657)

Background

Increasingly, women with stage 2 and 3 breast cancers receive neoadjuvant therapy, after which many are eligible for breast-conserving surgery (BCS). The question often arises as to whether BCS, if achievable, provides adequate local control. We report the results of local recurrence (LR) from the I-SPY 1 Trial in the setting of maximal multidisciplinary treatment where approximately 50 % of patients were treated with BCS.

Methods

We analyzed data from the I-SPY 1 Trial. Women with tumors ≥3 cm from nine clinical breast centers received neoadjuvant doxorubicin, cyclophosphamide and paclitaxel followed by definitive surgical therapy, and radiation at physician discretion. LR following mastectomy and BCS were analyzed in relation to clinical characteristics and response to therapy as measured by residual cancer burden.

Results

Of the 237 patients enrolled in the I-SPY 1 Trial, 206 were available for analysis. Median tumor size was 6.0 cm, and median follow-up was 3.9 years. Fourteen patients (7 %) had LR and 45 (22 %) had distant recurrence (DR). Of the 14 patients with LR, nine had synchronous DR; one had DR > 2 years later. Only four (2 % of evaluable patients) had LR alone. The rate of LR was low after mastectomy and after BCS, even in the setting of significant residual disease.

Conclusions

Overall, these patients at high risk for early recurrence, treated with maximal multidisciplinary treatment, had low LR. Recurrence was associated with aggressive biological features such as more advanced stage at presentation, where LR occurs most frequently in the setting of DR.     

The Role of Margin Status and Reexcision in Local Recurrence Following Breast Conservation Surgery

Introduction

Breast conservation surgery (BCS) results in survival equal to mastectomy for early-stage breast cancer. Ipsilateral breast tumor recurrence (IBTR) after BCS is thought to be related to margin status. At our institution, reexcision is performed only if tumor is at inked margin or with extensive disease close to multiple margins. The purpose of this study was to determine rates of reexcision and recurrences among BCS patients using this policy.

Methods

We performed an institutional review board-approved retrospective analysis of BCS patients who underwent surgery between January 2001 and June 2005. We identified patients who had a second breast excision within 8 weeks of the first, and those patients with an IBTR. Clinical and pathologic features of patients’ tumors were reviewed.

Results

We identified 543 patients who underwent BCS, 84 patients (15.5 %) underwent reexcision for margin status. The crude IBTR rate was 3.4 %, and the 5-year local recurrence-free survival of the reexcised group was 90.6 % compared with 97.4 % in the non-reexcised group (p = 0.0097). Of the 64 reexcision patients, 6 (9.4 %) had an IBTR versus 12 (2.6 %) of the 459 non-reexcised patients (p = 0.0151).

Discussion

Our reexcision rate is low compared with other reports. This results from a policy that defines “no tumor on ink” as an adequate margin for BCS, and the use of selective irradiation boosts based on margins assessed by our pathologists. Our local recurrence rate compares favorably with those seen in other studies while minimizing the need for additional operations. A higher IBTR rate after reexcision likely reflects tumor biology.     

Should Breast Density Influence Patient Selection for Breast-Conserving Surgery?

Background

In a previous study of the relationship between breast density and primary tumor features, we observed a higher mastectomy rate in patients with extremely dense breasts. Here we examine possible reasons for this finding.

Methods

Data were obtained from a prospectively maintained database of 1,056 invasive breast cancer patients from January 2005 to June 2007. Mammographic density was assigned by Breast Imaging-Reporting and Data System (BI-RADS) classification. Initial and final surgical procedures, and patient and tumor variables were recorded.

Results

Breast-conserving surgery (BCS) was attempted in 758 patients (72 %), 385 (51 %) of whom had preoperative magnetic resonance imaging (MRI). Initial BCS was less common among patients with the highest (BI-RADS 4) breast density compared to patients with less-dense breasts (52 vs. 74 %; p < 0.0001), but MRI use was more common (65 vs. 33 %; p < 0.0001). Adjusting for clinical and pathologic variables, patients with the highest breast density had 1.94-times (95 % confidence interval 1.44–2.62; p < 0.0001) the odds of initial mastectomy compared to patients with less-dense breasts. After initial BCS, 387 patients (51 %) had positive shaved margins, 96 (25 %) of whom converted to mastectomy. MRI did not correlate with the rate of positive margins overall or among those with dense breasts. Adjusting for clinical and pathologic variables, density did not predict margin status or conversion to mastectomy. In a multivariate model, age, histologic grade, extensive intraductal component, and multicentricity/multifocality were independently associated with conversion to mastectomy.

Conclusions

Density alone seems to influence the decision to proceed with initial mastectomy. When BCS was attempted, breast density was not associated with positive margins or conversion to mastectomy. A benefit of MRI in decreasing positive margins was not observed. These data do not support the use of breast density as a selection criterion for BCS.     

Calcifications on Mammogram Do Not Correlate with Tumor Size After Neoadjuvant Chemotherapy

Introduction

Calcifications can be indicative of malignancy, but calcifications also can be a byproduct of necrotic tissue as cancer cells die. Current treatment regimens require excision of calcifications. The objective of this study was to examine the correlation between the extent of calcification on mammography and actual tumor size after neoadjuvant chemotherapy (NAC) as well as magnetic resonance imaging (MRI) for comparison.

Methods

We retrospectively reviewed all patients at the University of California, San Diego, who underwent NAC for breast cancer between 2007 and 2013. Pearson correlation coefficients were computed between breast imaging and pathological measurements.

Results

There were 136 patients total. Average age was 51 years. Fifty-three patients had calcifications on imaging (calc+); 83 did not (calc?). In the calc? group, extent of disease measured by mammogram (MMG) and MRI correlated moderately well with pathological tumor size (0.46 and 0.48, p = not significant). In the calc+ group, MRI was more likely to correlate with pathology than MMG (0.55 vs. ?0.12, p = 0.01). Twenty-five calc+ patients had increased calcification after NAC; six of these had complete pathologic response. MRI correlated better with tumor size on pathology in patients with anti-HER2neu-based regimens than in patients with cytotoxic chemotherapy-alone regimens (0.88 vs. 0.4, p = 0.0001). MRI also is more accurate at predicting pathological tumor size in patients with triple negative disease (p = 0.002).

Conclusions

Magnetic resonance imaging correlated well while MMG calcification measurements correlated poorly with tumor size on final pathology. Extent of calcifications on diagnostic mammography may not be accurate in preoperative evaluation of breast cancers after NAC.     

Breast-Conserving Surgery After Tumor Downstaging by Neoadjuvant Chemotherapy is Oncologically Safe for Stage III Breast Cancer Patients

Background

We conducted a retrospective study to evaluate the local recurrence (LR) rate depending on the use of neoadjuvant chemotherapy (NCT) and to determine the oncologic safety of breast-conserving surgery (BCS) after NCT by comparing LR between patients treated with BCS and mastectomy in clinical stage III breast cancer patients.

Patients and Methods

Between 2004 and 2007, 166 patients underwent BCS or mastectomy after NCT (NCT group) and 193 patients underwent surgery first (surgery group) in clinical stage III breast cancer patients. Patients whose tumor size became ≤4 cm after NCT, 57 patients underwent mastectomy (mastectomy group) 39 patients underwent preplanned BCS (preplanned BCS group), and 33 patients underwent downstaged BCS (downstaged BCS group). The recurrence rates between the groups and risk factors for LR were analyzed.

Results

The 5-year LR-free survival rates were 93.6 % in the NCT group and 95.9 % in the surgery group (P = 0.108). In the NCT group, the 5-year LR-free survival rates were 96.3 % in the mastectomy group, 94.7 % in the preplanned BCS group and 90.9 % in the downstaged BCS group (P = 0.669). High expression of Ki-67 was a predictor of LR in patients in three groups (Hazard ratio 8.300, P = 0.049).

Conclusions

Our findings suggest that BCS after NCT in clinical stage III patients is oncologically safe in terms of LR if breast tumor size is ≤4 cm after NCT and Ki-67 is a predictor of LR after NCT.     

Cosmesis Outcomes for Sector Resection for Ductal Carcinoma In Situ (DCIS)

Background

Oncoplastic surgery allows wide excision of pathology with greater margins in breast-conserving surgery (BCS) without compromising the shape of the breast. Oncoplastic techniques were used to remove a sector of tissue to fully excise ductal carcinoma in situ (DCIS) with a large margin, with relocation of the breast tissue to maintain normal shape. We assessed patient satisfaction with breast cosmesis after surgery as well as patients’ psychosocial well-being.

Methods

A retrospective study was conducted of patients who underwent BCS alone for pure DCIS between 1995 and 2009, performed by two surgeons. The BREAST-Q questionnaire was modified for partial mastectomy to gain patients’ perspectives on cosmetic outcomes and satisfaction after surgery. The questionnaire also assessed the emotional and sexual well-being of the patients.

Results

Overall, there was a high level of patient satisfaction, with 52 of 55 women (94 %) satisfied or very satisfied with their cosmetic outcome after partial mastectomy.

Conclusions

Oncoplastic techniques used for partial mastectomies to provide greater oncological clearance resulted in a high level of patient satisfaction after surgery.     

Predictors of Local Recurrence in a Population-Based Cohort of Women with Ductal Carcinoma In Situ Treated with Breast Conserving Surgery Alone

Background

To identify prognostic indicators of local recurrence (LR) in patients with ductal carcinoma in situ (DCIS) of the breast treated with breast conserving surgery (BCS) alone.

Methods

A retrospective study was conducted of all women with pure DCIS, diagnosed 1985–1999, referred for tertiary oncologic opinion in British Columbia, treated with BCS without adjuvant radiotherapy. Kaplan–Meier local control (LC) and breast cancer specific survival (BCSS) estimates for the entire group were plotted. Stratified analyses identified subgroups with high Kaplan–Meier 10-year LR. Cox multivariate modeling was used to assess predictors of LR. Kaplan–Meier BCSS rates were compared between two cohorts: those who experienced LR and those who did not have LR.

Results

A total of 460 women comprised the study cohort. Median follow-up was 9.4 years. The 15-year LC and BCSS rates were 82% and 97%, respectively. Stratified analyses of LR identified comedo histology, high nuclear grade, tumor size >4 cm or indeterminate size, and positive margins to be associated with significantly higher LR risk, with 10-year LR risks approximating 15–30%. The 10-year BCSS rates for the LR group were 94% compared with 99% for the NoLR group. On Cox regression modeling, high nuclear grade, the presence of comedocarcinoma, and positive margins were significant factors for higher risk of LR.

Conclusions

Women with DCIS treated with BCS alone had higher LR risk, and those with a LR were more likely to die of breast cancer. Optimal local treatment is mandatory to minimize the risk of breast cancer death for women with this curable disease.     

Incidence and effect of calcifications after open-augmented Achilles tendon repair

Background and aims

The objective of this study was to analyse the incidence and effect on clinical outcome of post-operative Achilles tendon calcifications after open-augmented repair according to the Silfverskjöld technique.

Patients/methods

This retrospective study presents the results of follow-up examinations on 104 patients with Achilles tendon rupture who were treated according to the Silfverskjöld technique. Post-operative calcifications were identified by means of sonography, and clinical outcome was evaluated using the 100 points Thermann score. The average follow-up examination period was 3.7 years with an average patient age of 42.9 years. Two groups were identified and included those with (Group I) and those without (Group II) calcifications. Clinical outcome was evaluated using the Thermann score for both groups and was compared statistically by means of the two random sample t-test.

Results

Fifteen patients (Group I) developed tendon calcifications (14.4%) and 89 none (Group II). Group I scored 88.0 points and Group II 88.1 (good to very good outcome). There were no negative effects on clinical outcome (t = 0.98).

Conclusions

The incidence of tendon calcification after open-augmented repair of Achilles tendon rupture was 14.4% with no negative effects on clinical outcome as measured by the Thermann score.     

Breast-Conserving Surgery in BRCA1/2 Mutation Carriers: Are We Approaching an Answer?

Background

Approximately 10% of patients with breast cancer who are treated with breast-conserving surgery (BCS) develop an ipsilateral-breast tumor recurrence (IBTR). The optimal local therapy for women with BRCA-associated breast carcinoma remains controversial. We report the outcome of BCS in BRCA mutation carriers followed at a single institution.

Methods

A total of 54 women with BRCA1/2-associated breast cancer treated with BCS and whole breast radiotherapy were matched for age, tumor size, and time of surgery with 162 patients with sporadic breast cancer who had the same treatment between February 1994 and October 2007. Primary end points were cumulative incidence of IBTR and contralateral breast cancer (CBC). Median follow-up was 4 years for both groups.

Results

Median age was 36 and 37 years for mutation carriers and controls, respectively; mean tumor size was 1.8 cm in carriers and 1.9 cm in controls. Ten-year cumulative incidence of IBTR was 27% for mutation carriers and 4% for sporadic controls (hazard ratio 3.9; 95% confidence interval 1.1–13.8; P = 0.03). Ten-year cumulative incidence of CBC was 25% for mutation carriers and 1% for sporadic controls (P = 0.03).

Conclusions

Our data suggest that IBTR risk after BCS in BRCA1/2 mutation carriers is increased compared with patients who have sporadic breast cancer. Likewise, the risk of CBC seems to be increased in this group. These risks and the likelihood of developing new primary tumors should be discussed with carriers interested in breast conservation as well as when choosing risk-reducing strategies.     

Resection Margins in Ultrasound-Guided Breast-Conserving Surgery

Background

Few published studies have shown the benefits of intraoperative ultrasound in avoiding inadequate margins in breast-conserving surgery. The aim of this study is to quantify intraoperative ultrasound margin size and assess its relationship to tumor size, multifocality, palpability, histology, and presence of intraductal component.

Methods

Patients with breast cancer undergoing breast-conserving surgery in whom the operating surgeon visualized the tumor by ultrasound were included. Ultrasound margins measured intraoperatively were prospectively recorded and compared with pathology margins.

Results

Forty-five patients with 48 tumors were included. Twenty five patients (56%) had palpable tumors. Pathologic mean tumor size was 1.9 cm [95% confidence interval (CI) 1.6–2.2 cm, range 0.5–4.8 cm]. There was good correlation between closest margins recorded by ultrasound and pathology margins (r = 0.4674, P < 0.0008). Fourteen patients (31%) had margins re-excised intraoperatively, 12 of them in the direction of the closest pathological margin. Three patients (7%), all of whom had intraoperative re-excision, had a second operation for involved margins without residual cancer on pathological examination of the reoperative specimens. Ultrasound margins ≥0.5 cm achieved adequate pathology margins of ≥0.2 cm in 95% of margins. Overestimation of pathology margins by ultrasound measurement was significantly affected by multifocality (P = 0.0473). Tumor size, palpability, invasive lobular histology, and presence of ductal carcinoma in situ (DCIS) did not cause significant overestimation of pathology margins by ultrasound.

Conclusions

Intraoperative ultrasound may help maintain a low level of reoperation after breast-conserving surgery. Ultrasound margins <0.5 cm should be re-excised intraoperatively. Reliability of ultrasound in predicting the closest pathology margins was diminished in patients with multifocal tumors.     

Incidence and Consequence of Close Margins in Patients with Ductal Carcinoma-In Situ Treated with Mastectomy: Is Further Therapy Warranted?

Background

The impact of close margins in patients with ductal carcinoma-in situ (DCIS) treated with mastectomy is unclear; however, this finding may lead to a recommendation for postmastectomy radiotherapy (PMRT). We sought to determine the incidence and consequences of close margins in patients with DCIS treated with mastectomy.

Methods

The records of 810 patients with DCIS treated with mastectomy from 1996 through 2009 were reviewed. Clinical and pathologic factors were analyzed with respect to final margin status. Median follow-up was 6.3 years.

Results

Overall, 94 patients (11.7 %) had close margins (positive, n = 5; negative but ≤1 mm, n = 54; 1.1–2.9 mm, n = 35). Independent risk factors for close margins included multicentricity, pathologic lesion size ≥1.5 cm, and necrosis, but not age, use of skin-sparing mastectomy, or immediate reconstruction (p > 0.05). Seven patients received PMRT, and none had a locoregional recurrence (LRR). Among the remaining 803 patients, the 10-year LRR rate was 1 % (5.0 % for margins ≤1 mm, 3.6 % for margins 1.1–2.9 mm, and 0.7 % for margins ≥3 mm [p < 0.001]). The 10-year rate of contralateral breast cancer was 6.4 %. On multivariate analysis, close margins was the only independent predictor of LRR (p = 0.005).

Conclusions

Close margins occur in a minority of patients undergoing mastectomy for DCIS and is the only independent risk factor for LRR. As the LRR rate in patients with close margins is low and less than the rate of contralateral breast cancer, PMRT is not warranted except for patients with multiple close/positive margins that cannot be surgically excised.     

Factors Influencing Surgical and Adjuvant Therapy in Stage I Breast Cancer: A SEER 18 Database Analysis

Background

Randomized trials have shown no survival difference for patients with stage I breast cancer treated with mastectomy versus breast-conserving surgery (BCS) with radiotherapy (RT). RT is recommended after BCS in order to decrease local recurrence and mortality. We sought to evaluate the treatment trends in patients with stage I breast cancer.

Methods

We used the Surveillance, Epidemiology, and End Results (SEER) database to identify 194,860 women with stage I breast cancer diagnosed from 1988 to 2007. We evaluated factors that were associated surgical treatment and the utilization of RT after BCS.

Results

There was a progressive decline in the proportion of patients with stage I breast cancer who were treated with mastectomy from 1998 to 2007. Significant predictors for being treated with mastectomy included single/divorced women (p = 0.007), white race (p < 0.001), estrogen receptor negativity (p < 0.001), earlier year of diagnosis (p < 0.001), smaller tumor size (p < 0.001), and region (p < 0.001). Twenty percent of the BCS cohort did not receive RT, and this proportion did not change over time. Significant predictors for not receiving RT included small tumor size (p < 0.001), African American race (p < 0.001), increasing age (p < 0.001), single/divorced women (p < 0.001), estrogen receptor negativity (p < 0.001), and region (p < 0.001). The survival for patients treated with BCS and RT was significantly higher than for those who did not receive RT (p < 0.001).

Conclusions

The use of BCS for the treatment of stage I breast cancer increased over time. A constant proportion of patients did not receive RT after BCS. Omission of RT in BCS is associated with an increase in mortality.     

Are Breast Cancer Subtypes Prognostic for Nodal Involvement and Associated with Clinicopathologic Features at Presentation in Early-Stage Breast Cancer?

Background

Breast cancer subtypes (BCS) determined from immunohistochemical staining have been correlated with molecular subtypes and associated with prognosis and outcomes, but there are limited data correlating these BCS and axillary node involvement. This study was conducted to assess whether BCS predicted for nodal metastasis or was associated with other clinicopathologic features at presentation.

Methods

Patients with stage I/II disease who underwent breast-conserving surgery and axillary surgical assessment with available tissue blocks underwent a institutional pathological review and construction of a tissue microarray. The slides were stained for estrogen receptor, progesterone receptor, and HER-2/neu (HER-2) for classification into BCS. Nodal involvement and other clinicopathologic features were analyzed to assess associations between BCS and patient and tumor characteristics. Outcomes were calculated a function of BCS.

Results

The study cohort consisted of 453 patients (luminal A 48.6 %, luminal B 16.1 %, HER-2 11.0 %, triple negative 24.2 %), of which 22 % (n = 113) were node positive. There were no significant associations with BCS and pN stage, node positivity, or absolute number of nodes involved (p > 0.05 for all). However, there were significant associations with subtype and age at presentation (p < 0.001), method of detection (p = 0.049), tumor histology (p < 0.001), race (p = 0.041), and tumor size (pT stage, p < 0.001) by univariate and multivariate analysis. As expected, 10-year outcomes differed by BCS, with triple negative and HER-2 subtypes having the worse overall (p = 0.03), disease-free (p = 0.03), and distant metastasis-free survival (p < 0.01).

Conclusions

There is a significant association between BCS and age, T stage, histology, method of detection, and race, but no associations to predict nodal involvement. If additionally validated, these findings suggest that BCS may not be a useful prognostic variable for influencing regional management considerations.     

Increased Use of Partial-Breast Irradiation Has Not Improved Radiotherapy Utilization for Early-Stage Breast Cancer

Background

Radiotherapy (RT) reduces local recurrence after breast-conserving surgery (BCS) for breast cancer, but under-utilization of RT has been reported. Accelerated partial-breast irradiation (PBI) improves RT accessibility, but it is uncertain if this has improved RT utilization.

Methods

The Surveillance, Epidemiology and End Results registry was used to identify women who underwent BCS for stage 0 or 1 breast cancer from 2000 to 2009. Temporal trends in RT utilization and RT modality were determined. Chi-square analysis and multivariate logistic regression identified predictors of RT utilization and modality.

Results

Of 180,219 study patients, 131,343 (73 %) received RT; 123,703 (94 %) of RT recipients received whole-breast irradiation (WBI) and 6,251 (5 %) received PBI. PBI rates increased dramatically during the study period (0.32 % in 2000 vs. 6.5 % in 2009), but overall RT utilization remained relatively stable because of a decline in WBI (69.8 % in 2000 vs. 62.4 % in 2009). RT utilization was unchanged in rural counties, and declined for women <40 and ≥70 years of age, and for Native American, Asian and Hispanic patients. White and Black women used PBI most frequently (4 % each) and were the only race groups with improved RT utilization over time. Predictors of RT usage included age, race, marital status, tumor size, grade, hormone receptor status, lymph node evaluation, geographic region, metropolitan status, education, and employment status.

Conclusions

Women who undergo RT are opting for PBI more frequently, but the increased use of this modality has not improved overall RT utilization for patients with early-stage breast cancer.     

Outcomes of endoscopic resection for high-grade dysplasia and esophageal cancer

Background

Endoscopic resection (ER) is an important advance in the management of esophageal tumors. It has been used successfully for superficial esophageal cancer and high-grade dysplasia (HGD) arising out of Barrett epithelium.

Methods

From a single institution within the Department of Surgery, patients who underwent ER for esophageal tumors between December 2001 and January 2012 were evaluated. Demographic, clinical, and pathologic variables were collected and reviewed.

Results

We identified 81 patients who underwent ER for esophageal lesions. Median patient age was 69 years, and the median follow-up was 3.25 years. In patients with HGD, at the time of last endoscopy, the complete eradication rate of HGD was 84 % and cancer-specific survival was 100 %. During surveillance, one patient developed an invasive carcinoma that required endoscopic therapy. Patients with T1a and negative deep margins on ER had a recurrence-free and cancer-specific survival of 100 %. There were seven patients with T1b and negative margins on ER. Three patients underwent esophagectomy; final pathology revealed no residual malignancy or lymph node metastasis. Two patients had definitive chemoradiation, and two patients were observed. To date, there has been no cancer recurrence. In all patients who underwent ER, there was one episode of bleeding that required endoscopic treatment and admission for observation.

Conclusions

ER can be performed safely and can adequately stage and often treat patients with HGD and superficial cancers. Patients with HGD and T1a disease with negative margins are cured with ER alone. Observation and surveillance may be an option for select patients with low-risk, early submucosal disease (T1b) and negative margins.     

Efficacy and Patient Satisfaction of Breast Conserving Therapy for Central Breast Cancer by the B Technique

Purpose

To evaluate the oncologic safety and cosmetic results after breast cancer surgery for central breast cancer by the B technique.

Methods

Seventy women with operable breast cancer located in the central portion of the breast that had received resection surgery with the B technique were recruited. The primary outcome was the oncological safety, quantified as rate of positive resection margins and the cosmetic outcome evaluated by postsurgical self-assessment of the cosmetic outcome via questionnaire. The median follow-up period was 61.4 months (range 7.9–142.6 months).

Results

With one exception all patients had T1–2 tumors less than 5 cm in diameter. Most patients had invasive ductal breast cancers (57.1 %), followed by ductal carcinoma-in situ (27.1 %) and invasive lobular breast cancers (8.6 %). The incidence of positive resection margins was 17.1 %. No local tumor recurrence occurred during follow-up; one patient had distant metastases. In total, 80 % of the patients reported that the cosmetic results met or exceeded their expectations.

Conclusions

The B technique is a safe breast conservation surgery for the excision of tumors located in the central portion of the breast and yields a high rate of satisfactory cosmetic results.     

Molecular Staging of Surgical Margins in Oral Squamous Cell Carcinoma Using Promoter Methylation of p16INK4A, Cytoglobin, E-cadherin, and TMEFF2

Background

Local recurrence in oral squamous cell carcinoma (OSCC) despite clear surgical margins may indicate the presence of residual, sub-microscopic disease. Molecular assessment of surgical margins may provide a greater prognostic sensitivity compared to histopathology. We aimed to determine whether promoter methylation in deep and mucosal resection margins can predict recurrence in OSCC.

Methods

Forty-eight consecutive OSCC cases were recruited and a 5 mm³ tumor sample plus 5 deep and 5 mucosal margin samples were snap frozen. Clinical, pathological, adjuvant therapy, and outcome data were recorded. Tumors were informative if >5 % promoter methylation was found for ≥1 of 4 genes using qMSP. Margins were declared molecularly positive if >1 % promoter methylation was found in any margin.

Results

Thirty (63 %) of 48 cases were methylation informative. Mucosal margin samples were largely positive for methylation (26 of 30, 87 %), indicating the presence of field cancerization. Methylation at ≥1 gene promoters in ≥1 deep margin correlated with the presence of close/involved mucosal margins (P = 0.027) and increased pT status (P = 0.027) but not the status of deep margins, recurrence, or survival.

Conclusions

The current gene panel did not add prognostic information to histopathological reporting of resection margins. Future efforts should concentrate on improving gene selection, informativity, and assay performance in the patient group with intermediate indications for adjuvant therapy.     

Predictors of margin status after breast-conserving operations in an underscreened population

Purpose

Negative margins after lumpectomy remain a prominent issue in breast surgery. The current study was performed to evaluate patient-related variables that affect risk for positive margins in an underscreened population.

Methods

A retrospective review was performed of all patients who underwent breast-conserving operations from 2001 to 2010. Sociodemographic, clinical, and treatment variables were evaluated. One millimeter from tumor to inked margin was considered a negative margin. Univariate and multivariate analyses were performed to identify variables which affect margin status after a lumpectomy.

Results

Over the time period evaluated, 69 patients had positive margins (31 %) and 155 (69 %) had negative margins. Overall use of screening mammography was poor (36 %). In unadjusted analysis, patients with positive margins were less likely to have undergone screening mammography (p?=?0.003) and presented with a palpable mass (p?=?0.01). Histopathologic variables which predicted increased risk for positive margins included larger pathologic size, greater number of pathologically involved lymph nodes, higher pathologic stage, presence of lymphovascular invasion (LVI) and extensive intraductal component (EIC), p?<?0.05. In multivariate analysis, clinical stage, poor histologic grade, LVI, and EIC were associated with positive margins (p?<?0.05). By contrast, use of preoperative chemotherapy was associated with attaining negative margins (p?<?0.05).

Conclusions

Factors associated with positive margins after lumpectomy included poor histologic grade, LVI, and EIC. Use of preoperative chemotherapy was the strongest independent predictor of lower risk for positive margins.     

Timing and Pattern of Recurrence in Ovarian Cancer Patients with High Tumor Dissemination Treated with Primary Debulking Surgery Versus Neoadjuvant Chemotherapy

Purpose

To compare the timing and pattern of recurrence in patients with advanced ovarian cancer (AOC) receiving primary debulking surgery (PDS) versus neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS).

Methods

We retrospectively evaluated a consecutive series of 175 stage IIIC–IV epithelial ovarian cancer patients, with diffuse peritoneal carcinomatosis documented at initial surgical exploration. Forty patients received complete PDS, and the remaining 135 were treated with NACT followed by IDS with absent residual tumor after surgery.

Results

No differences were observed in the distribution of clinical pathological characteristics at the time of diagnosis between the two groups. The median follow-up was 31 months (range 9–150 months). We observed 20 (50.0 %) recurrences in the PDS group compared to 103 (76.3 %) in the IDS group (p = 0.001). Duration of primary platinum-free interval (PFI) was shorter in IDS compared to PDS group (13 vs. 21 months, respectively; p = 0.014). A significantly higher percentage of patients in the IDS group experienced platinum-resistant recurrences (35.9 vs. 5.0 %; p = 0.006) and carcinomatosis at the time of relapse (57.3 vs. 20.0 %; p = 0.0021). Finally, in women with platinum-sensitive recurrence, we observed a shorter secondary PFI in the IDS compared to PDS group (p = 0.006).

Conclusions

We documented a better behavior of recurrent disease in AOC patients with diffuse peritoneal carcinomatosis treated with complete PDS compared to women submitted to NACT followed by IDS with no residual tumor after surgery.     

Surgical Outcome after Neoadjuvant Chemotherapy and Bevacizumab: Results from the GeparQuinto Study (GBG 44)

Purpose

Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, has shown increased pathological complete response rates when added to neoadjuvant chemotherapy. In various cancer types, bevacizumab treatment was accompanied by an increased risk of bleedings and other surgical complications. We assessed associated surgical complications.

Methods

In the GeparQuinto trial, 1,948 patients were randomized to receive four cycles epirubicin/cyclophosphamide (EC, 90/600 mg/m² q3w) followed by four cycles docetaxel (D, 100 mg/m² q3w) each with (ECB-DB) or without (EC-D) bevacizumab (B, 15 mg/kg q3w) concurrent with chemotherapy. Surgery had to be performed not earlier than 28 days after the last bevacizumab infusion, but within days 21 and 35 after the last chemotherapy.

Results

In 743 (38.1 %) patients, a surgical complication (bleedings, hematomas, necrosis, wound infections, abscess) was documented prospectively. Baseline characteristics of the patients were well balanced between both arms. The breast-conserving surgery (BCS) rate (N = 502) was 69.1 % (EC-D) and 71.9 % (ECB-DB; p = 0.464). The first surgical procedure was performed at a median of 29 (EC-D) and 34 days (ECB-DB) after last chemotherapy with or without bevacizumab infusion (p < 0.001). Surgical complications were documented in 38 (10.9 %; EC-D) and 59 (15.0 %; ECB-DB) patients (p = 0.103). Surgical complications were significantly higher after ECD-DB only in patients treated with BCS (N = 53; p = 0.029) or in those requiring repeat surgery in order achieve clear margins (N = 23; p = 0.037) compared to the EC-D group.

Conclusions

Addition of bevacizumab to neoadjuvant chemotherapy might be associated with an increased risk for surgical complications in patients treated with BCS or after repeated surgeries.