Effect of Margin Width on Local Recurrence in Triple-Negative Breast Cancer Patients Treated with Breast-Conserving Therapy

Background

The effect of increasing negative margin width after breast-conserving therapy (BCT) on local recurrence (LR) is controversial. LR rates vary by subtype, with the highest rates seen in triple-negative breast cancer (TNBC). This study examined LR rates in relationship to margin width in TNBC treated with BCT.

Methods

Women with TNBC who underwent BCT between 1999 and 2009 were identified. Margins were defined as positive (ink on tumor), 0.1–2.0, and 2 mm. Patients with positive margins were excluded. Statistical comparisons were by t test, Fisher’s exact test, and Wilcoxon rank sum test. Cumulative incidence of LR was compared by competing-risks methodology.

Results

Of 535 cancers, 71 had margins ≤2 mm and 464 had margins >2 mm. At a median follow-up of 84 months (range 8–165 months), there were 37 local, 18 regional, and 77 distant recurrences or deaths as first events. Ten patients had a locoregional recurrence before planned radiotherapy and were excluded from cumulative incidence analyses. The cumulative incidence of LR at 60 months for margins ≤2 mm was 4.7 % (95 % confidence interval 0–10.0) and for >2 mm was 3.7 % (1.8, 5.5) (p = 0.11). After controlling for chemotherapy and tumor size, there was no difference in LR between the two margin groups (p = 0.06). A difference in the risk of distant recurrence or death was not observed (p = 0.53).

Conclusions

Margin width of >2 mm was not associated with reduced LR rates. These data support a negative margin definition of no ink on tumor, even in this high-risk TNBC cohort.     

Breast-Conserving Therapy: A Viable Option for Young Women with Early Breast Cancer—Evidence from a Prospective Study

Background

This study evaluated the security of breast-conserving treatment (BCT) in young patients and the effect of regional radiation therapy on young patients with 1–3 positive nodes (N+) treated with BCT.

Methods

In this prospective concurrent controlled study, 164 patients were defined as the BCT group, and regional radiation therapy was delivered to patients with 1–3 N+. Modified radical mastectomies (MRMs) were performed on 224 patients without regional radiation therapy.

Results

The 9-year local recurrence (LR) rate of the BCT was 7 %, compared with 3 % in the MRM group (p = 0.055). The 9-year regional recurrence (RR) rate was 6 % for the BCT group and 12 % for the MRM group (p = 0.048). The distant metastasis (DM)-free and breast cancer-specific survival rates were similar between the two groups. RR was an independent prognostic factor for DM [hazard ratio 3.27; 95 % confidence interval (CI) 1.726–6.208] and breast cancer-specific survival (hazard ratio 5.814; 95 % CI 2.690–12.568), whereas LR was not an independent prognostic factor for DM or breast cancer-specific survival.

Conclusions

Young patients treated with BCT have a higher LR rate than that of MRM. However, LR has no detrimental effect on DM-free and breast cancer-specific survival rates, whereas RR is a strong risk factor of DM and death. Regional radiation therapy for young patients with 1–3 N+ may reduce RR and improve survival rates.     

Breast-Conserving Therapy Achieves Locoregional Outcomes Comparable to Mastectomy in Women with T1-2N0 Triple-Negative Breast Cancer

Background

Conflicting data exist regarding optimum local therapy for early-stage triple-negative breast cancer (TNBC). We examined outcomes according to local treatment type in a large cohort of node-negative TNBC patients.

Methods

A total of 1,242 consecutive patients with TNBC treated at a single institution from 1999 to 2008 were identified. Of these, 646 with pathologic stage T1-2N0 TNBC underwent breast-conserving therapy (BCT) (N = 448) or total mastectomy (TM) without postmastectomy radiation (N = 198) and comprised the study population. Locoregional recurrence (LRR), distant metastasis (DM), and overall recurrence were investigated with a competing risk analysis using Gray’s test and multivariable Fine and Gray competing risk regression. Overall survival was assessed using standard Kaplan–Meier methods and a Cox proportional hazards analysis.

Results

Median follow-up was 78.3 months (range 1–156). Eight-one percent of patients received adjuvant chemotherapy. TM patients were younger, were more likely to have lymphovascular invasion, and had larger tumors than patients undergoing BCT (all P ≤ 0.05). The 5-year cumulative incidence of LRR was 4.2 and 5.4 % for patients undergoing BCT and TM, respectively. There was no significant difference in LRR, DM, overall recurrence, disease free survival, or overall survival between groups on univariate analysis, or after adjusting for other variables in multivariate models. Lack of chemotherapy and high tumor stage independently predicted for decreased overall survival (both P < 0.001).

Conclusions

A low, 5-year risk of LRR (4.7 %) was achieved in a large group of women with T1-2N0 TNBC treated with multimodality therapy. BCT was as equally effective as TM for local and distant control.     

Safe Negative Margin Width in Breast Conservative Therapy: Results from a Population with a High Percentage of Negative Prognostic Factors

Background

There remains a controversy in the literature regarding adequate width of negative surgical margins in breast conservative therapy (BCT). It is now advocated that no tumor on an inked margin is a safe negative margin. Majority of studies on the outcomes of BCT had patients with favorable prognostic factors. Pakistani population has a high expression of unfavorable prognostic factors. The objective of this study was to determine a safe negative margin width in Pakistani population that undergoes BCT.

Methods

A total of 603 patients with identifiable surgical margins underwent BCT from 1997 to 2009 in Shaukat Khanum Cancer Hospital. Patients were divided into close (≤2 mm), free (>2–10 mm), and wide (>10 mm) margin groups. Locoregional recurrence was defined as recurrence within the operated breast, ipsilateral axilla, or supraclavicular or internal mammary lymph nodes. Locoregional recurrence-free survival was calculated from the date of surgery to the date of locoregional recurrence. Five-year locoregional recurrence-free survival was determined for margin groups. Univariate and multivariate Cox proportional hazard analyses were performed to determine independent predictors of locoregional recurrence.

Results

A total of 415 (69 %) patients were <50 years of age. There were 82 (15 %) T3/T4, 337 (56 %) poorly differentiated, and 238 (39 %) ER/PR ?ve tumors. Nodal positivity was present in 314 (52 %) patients. The actual number of locoregional recurrences was 16 (12 %), 8 (3 %), and 10 (4.6 %), respectively (P = 0.002). Expected 5-year locoregional recurrence-free survival was 90, 97, and 96 %, respectively (P = 0.002). On multivariate analysis, tumor size, nodal involvement, and negative margin width were independent predictors of locoregional recurrence.

Conclusion

A negative margin width of 2 mm might represent an adequate negative margin width in the Pakistani population undergoing breast conservative therapy.     

Outcomes and Predictive Factors for Salvage Therapy After Local–Regional Recurrence Following Neoadjuvant Chemotherapy and Breast Conserving Therapy

Background

There are few data addressing local–regional recurrence (LRR) and salvage therapies in patients treated with neoadjuvant chemotherapy (NCT) compared to those treated with surgery first. We characterize the clinical course and predictive features of salvage treatment for LRR after breast conserving therapy (BCT) analyzed by initial treatment.

Methods

We identified 1,589 patients who underwent BCT; 1,141 (72 %) patients underwent initial surgery, and 448 (28 %) received NCT. Kaplan–Meier and Cox regression analyses were performed to analyze factors associated with overall survival (OS), local control (LC) of recurrence, and distant metastasis-free survival (DMFS) following LRR.

Results

56 patients had a LRR, for a crude recurrence rate of 3 %. For patients with potentially curable recurrence (excluding distant metastases within 3 months of LRR), the 5-year OS, LC, and DMFS rates were 52, 77, and 69 %. On multivariate analysis, initial pathologically negative node status and use of surgery for salvage were significant factors associated with higher OS. Additionally, older age was associated with higher LC rates after salvage. Estrogen receptor-positive disease and surgery for LRR were associated with reduced risk of distant metastases; regional recurrence and use of initial adjuvant chemotherapy were associated with increased risk of distant metastases. For each of these endpoints, the addition of NCT to the multivariate model did not approach significance.

Conclusions

LRR is an uncommon event after BCT and many patients with LRR remain curable (5-year OS >50 %). Our data indicate that NCT does not compromise salvage after LRR, providing further assurance that this strategy is safe for appropriately selected breast cancer patients.     

Predictive Factors and Patterns of Recurrence in Patients with Triple Negative Breast Cancer

Background

We investigated the outcomes of patients with triple negative breast cancer ([TNBC] = estrogen receptor negative, progesterone receptor negative, and HER2 nonamplified).

Methods

We identified 414 patients with stage I–III TNBC treated between 1999 and 2008. Data included patient/tumor characteristics, surgical, systemic, and radiation treatment received, and breast cancer-specific survival. Data were compared using Chi square, Fisher exact test, and logistic regression. A p value <.05 was considered significant.

Results

The cohort included 414 patients (mean age 53.8 ± 12.5 years) with a mean follow-up of 68.2 ± 36.4 months. Of 414 patients, 304 (73.4 %) had no evidence of recurrence, while 110 (26.6 %) had recurrent disease, including 19 (17.3 %) with isolated locoregional recurrence, 70 (63.6 %) with isolated distant recurrence, and 21 (19.1 %) with both. Of 91 patients with distant recurrences, lung was most common (n = 38), followed by brain (n = 32), bone (n = 31), and liver (n = 29). Factors significantly associated with recurrence included increasing tumor size, positive nodal status, increasing stage, and type of chemotherapy (adjuvant vs neoadjuvant). After controlling for all potential confounders in multivariate stepwise regression, these same factors were also found to be independent predictors of recurrence. In the survival analysis, these same factors, in addition to receipt of radiation were found to be predictive of survival.

Conclusions

Approximately 25 % of patients with TNBC experienced a locoregional and/or distant recurrence, resulting in greater than 75 % breast cancer-specific mortality for those who experienced a distant recurrence. The lack of targeted therapy for this aggressive breast cancer subtype likely contributed to this finding.     

What is the Significance of the Circumferential Margin in Locally Advanced Rectal Cancer After Neoadjuvant Chemoradiotherapy?

Background

The circumferential resection margin (CRM) is highly prognostic for local recurrence in rectal cancer surgery without neoadjuvant treatment. However, its significance in the setting of long-course neoadjuvant chemoradiotherapy (nCRT) is not well defined.

Methods

Review of a single institution’s prospectively maintained database from 1998 to 2007 identified 563 patients with locally advanced rectal cancer (T3/T4 and/or N1) receiving nCRT, followed after 6 weeks by total mesorectal excision (TME). Kaplan-Meier, Cox regression, and competing risk analysis were performed.

Results

The authors noted that 75 % of all patients had stage III disease as determined by endorectal ultrasound (ERUS) and/or magnetic resonance imaging (MRI). With median follow-up of 39 months after resection, local and distant relapse were noted in 12 (2.1 %) and 98 (17.4 %) patients, respectively. On competing risk analysis, the optimal cutoff point of CRM was 1 mm for local recurrence and 2 mm for distant metastasis. Factors independently associated with local recurrence included CRM ≤1 mm, and high-grade tumor (p = 0.012 and 0.007, respectively). CRM ≤2 mm, as well as pathological, nodal, and overall tumor stage are also significant independent risk factors for distant metastasis (p = 0.025, 0.010, and <0.001, respectively).

Conclusion

In this dataset of locally advanced rectal cancer treated with nCRT followed by TME, CRM ≤1 mm is an independent risk factor for local recurrence and is considered a positive margin. CRM ≤2 mm was associated with distant recurrence, independent of pathological tumor and nodal stage.     

The Association of Surgical Margins and Local Recurrence in Women with Early-Stage Invasive Breast Cancer Treated with Breast-Conserving Therapy: A Meta-Analysis

Purpose

There is no consensus on what constitutes adequate negative margins in breast-conserving therapy (BCT). We systematically review the evidence on surgical margins in BCT for invasive breast cancer to support the development of clinical guidelines.

Methods

Study-level meta-analysis of studies reporting local recurrence (LR) data relative to final microscopic margin status and the threshold distance for negative margins. LR proportion was modeled using random-effects logistic meta-regression.

Results

Based on 33 studies (LR in 1,506 of 28,162), the odds of LR were associated with margin status [model 1: odds ratio (OR) 1.96 for positive/close vs negative; model 2: OR 1.74 for close vs. negative, 2.44 for positive vs. negative; (P < 0.001 both models)] but not with margin distance [model 1: >0 mm vs. 1 mm (referent) vs. 2 mm vs. 5 mm (P = 0.12); and model 2: 1 mm (referent) vs. 2 mm vs. 5 mm (P = 0.90)], adjusting for study median follow-up time. There was little to no statistical evidence that the odds of LR decreased as the distance for declaring negative margins increased, adjusting for follow-up time [model 1: 1 mm (OR 1.0, referent), 2 mm (OR 0.95), 5 mm (OR 0.65), P = 0.21 for trend; and model 2: 1 mm (OR 1.0, referent), 2 mm (OR 0.91), 5 mm (OR 0.77), P = 0.58 for trend]. Adjustment for covariates, such as use of endocrine therapy or median-year of recruitment, did not change the findings.

Conclusions

Meta-analysis confirms that negative margins reduce the odds of LR; however, increasing the distance for defining negative margins is not significantly associated with reduced odds of LR, allowing for follow-up time. Adoption of wider relative to narrower margin widths to declare negative margins is unlikely to have a substantial additional benefit for long-term local control in BCT.     

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.     

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.     

Is limited surgery justified in the treatment of T1 colorectal cancer?

Background

Surgical treatment of colorectal cancer (CRC) should be aimed primarily at achieving a combination of surgical-oncologic radicalness and the highest possible quality of life. In recent years, surgical therapy for T1 CRC has tended toward less radical interventions. The question regarding changes in survival and recurrence rates still is unanswered.

Methods

A retrospective medical chart review of patients surgically treated in our department for T1 CRC from January 1990 to December 2010 (n = 223) was performed. Charts were reviewed for tumor-specific parameters, local recurrence, distant metastasis, and patient survival. The different treatment options used were strictly separated for a more detailed workup.

Results

Radical resection (RR) was performed for 57.1 %, local resection (LR) for 14.8 %, and an endoscopic approach (EA) for 28.1 % of the study population. After receipt of the histology report, 35.7 % of the patients initially resected nonradically underwent reoperation, mostly using RR. Seven patients experienced a local recurrence over time (3.6 %): one after initial RR, three after LR, and three after EA. Systemic recurrence occurred for nine patients (4.6 %) over time, six of whom had undergone initial RR. High-risk criteria were shown for 20 T1 CRCs. For 60 % (12/20) of the patients, initial RR was performed. Radical reoperation was performed for 75 % of the nonradically treated high-risk tumors. One high-risk patient without reoperation experienced metastatic disease over time. The 5-year overall survival rate was 87.2 %, itemized for the defined subgroups as follows: 83.9 % for RR, 82.8 % for LR, and 58.2 % for EA.

Conclusion

Patients with T1 CRC had a distinctly higher incidence of local recurrence after EA or LR. Explicit workup in terms of risk classification is crucial to reducing the risk of local and systemic recurrence. A nonradical approach should be only a second option for patients with T1 CRC, namely, those solely in clearly low-risk situations or those with distinct comorbidities.     

Impact of Multifocality and Lymph Node Metastasis on the Prognosis and Management of Microinvasive Breast Cancer

Background

There are few data on the long-term outcome of patients with microinvasive (T1mi) breast cancer. Moreover, predictors of lymph node involvement and the impact of multifocal microinvasion are not well understood.

Methods

Patients with T1mi cancer, defined as tumors ≤1 mm, surgically managed at our institute and who underwent axillary lymph node evaluation were identified. Specimen slides were independently reviewed. Multivariate analysis was used to identify factors predictive of lymph node involvement.

Results

Forty-five patients with T1mi cancer were identified. Median patient age was 52 years, and median size of in situ disease was 4 cm. Nine tumors (20.0 %) had more than one focus of microinvasion. Lymph nodes metastasis were identified in 9 patients: 1 macrometastasis (2.2 %), 4 micrometastases (8.9 %), and 4 isolated tumor cells (8.9 %). Seven of 9 patients with lymph node involvement underwent adjuvant chemotherapy. Estrogen receptor–negative invasive disease was a significant predictor of lymph node metastasis by multivariable analysis (p < 0.02). There was also a trend toward lymph node involvement in patients with multifocal microinvasion compared to unifocal disease (33.3 vs. 16.7 %, respectively). At a median follow-up of 83 months, 3 patients (6.3 %) had disease recurrence (1 local, 1 distant, 1 local and distant). All patients with recurrence initially had tumor-free lymph nodes and only one focus of microinvasion.

Conclusions

Microinvasive breast cancer clearly has the ability to metastasize and recur, but in this series, only 2 % of patients with nodal macrometastasis. Only two patients experienced local recurrence, neither of whom had lymph node metastasis. The importance of identifying nodal micrometastasis in T1mi disease needs to be further explored.     

Impact of Circumferential Resection Margin Distance on Locoregional Recurrence and Survival after Chemoradiotherapy in Esophageal Squamous Cell Carcinoma

Background

Close circumferential resection margin (CRM) is an established predictor for locoregional recurrence (LR) in rectal cancer but remains controversial in esophageal malignancy. As yet, little is known about the significance of CRM after chemoradiotherapy (CRT), especially in squamous cell carcinoma (SCC). This study investigated the relationship between CRM distance and recurrence after neoadjuvant CRT in esophageal SCC patients.

Methods

Between 1997 and 2005, esophageal SCC patients who underwent surgery after neoadjuvant CRT and with pathology stage T3N0M0 and T3N1M0 (metastatic lymph nodes <2) were selected. CRM distance was reassessed and divided into three groups (group 1: CRM >1 mm, group 2: uninvolved CRM but <1 mm, group 3: CRM involved).

Results

The cohort comprised 145 male and 6 female patients with mean age of 57 years. There were 74, 51, and 26 patients in group 1, 2, and 3, respectively. With median follow-up period of 50 months, LR developed in 30.5% of patients. Both group 2 and group 3 had significantly higher LR than group 1 (37 and 42% vs. 21%, P < 0.05). Meanwhile, mean time from operation to recurrence was also significantly shorter in group 2 and group 3 than in group 1 (267 and 269 days versus 402 days, P < 0.05). Five-year disease-specific survival (DSS) was highest in group 1 (40%). Despite the similarity in LR, 5-year DSS significantly differed between group 2 and group 3 (22 vs. 7%, P < 0.05). The higher rate of distant recurrence (DR) and concomitant LR + DR in group 3 accounted for the survival difference.

Conclusion

In ypT3 esophageal SCC patients, CRM distance provides useful information for risk stratification in cancer recurrence and survival.     

Single HCC in Cirrhotic Patients: Liver Resection or Liver Transplantation? Long-term Outcome According to an Intention-to-treat Basis

Background

Compensated cirrhotic patients with single hepatocellular carcinoma (HCC) ≤5 cm may benefit from both liver resection (LR) and liver transplantation (LT); however, the better 10-year actuarial survival of the two treatments remains unclear. We aimed to assess the long-term outcome of cirrhotic patients with single HCC ≤5 cm treated either with LR or LT on an intention-to-treat basis.

Methods

A total of 217 cirrhotic patients with single HCC ≤5 cm were evaluated at our department: 95 were treated with LR (LR group), and 122 were included on the waiting list for LT (LT group). Patients in the LR group were divided into very early HCC (tumor size ≤2 cm) and early HCC (tumor size >2 cm). Median follow-up was 5.3 (range 0.1–18) years.

Results

Tumor recurrence was 72 % in the LR group versus 16 % in the LT group (p < 0.001). 1-, 5-, and 10-year cumulative risk of recurrence was 18, 69, and 83 % in the LR group versus 4, 18, and 20 % in the LT group (p < 0.001). Ten-year actuarial survival was 33 % in the LR group versus 49 % in the LT group (p = 0.002). At HCC recurrence, 27.3 % were included on the waiting list for salvage transplantation (very early HCC group) versus 15.1 % (early HCC group) (p = 0.2). After salvage transplantation, HCC recurrence was 0 % (very early HCC group) versus 40 % (early HCC group) (p = 0.2). No significant differences were observed in 1-, 5-, and 10-year actuarial survival between the very early HCC group and the LT group (95, 55, and 50 % vs. 82, 62, and 50 %).

Conclusions

LR should be the treatment of choice for cirrhotic patients with very early HCC.     

Outcome Analyses of Unusual Site Neck Recurrence in Oral Cavity Cancer

Aim

To understand the frequency, clinical significance, and benefits of salvage therapy in oral cavity squamous cell carcinoma (OSCC) patients with regional nodal recurrence at unusual sites (prelaryngeal area, parotid area, and retropharyngeal area).

Methods

We examined 178 patients with neck recurrence at levels I–V (usual group) and 26 patients outside levels I–V (unusual group). The 5-year survival rates served as the main outcome measure.

Results

Of the 26 unusual group patients, the neck recurrence sites were as follows: 5 at the prelaryngeal area, 13 at the parotid area, and 8 at the retropharyngeal area. Multivariate analyses demonstrated that poor differentiation, pN2, extracapsular spread (ECS), tumor depth ≥10 mm, relapse time ≤10 months, local recurrence, neck recurrence at unusual sites, and distant metastases were independent prognostic factors for 5-year disease-specific survival (DSS), whereas pN2, ECS, tumor depth ≥10 mm, relapse time ≤10 months, neck recurrence at unusual sites, and distant metastases were independent prognostic factors for 5-year overall survival (OS). The 6-month and 18-month survival rates after the N-relapse date for the salvaged-usual group, the salvaged-unusual group, and the nonsalvaged patients were 73 %/46 %, 40 %/0 %, and 10 %/0 % (P < 0.0001), respectively [DSS: salvaged-unusual group (hazard ratio/95 % confidence interval), 2.060/1.058–4.008, P = 0.033; salvaged-usual group, 6.420/4.340–9.496, P < 0.001; OS: salvaged-unusual group, 2.100/1.080–4.081, P = 0.029; salvaged-usual group, 6.514/4.418–9.606, P < 0.001].

Conclusions

Our findings demonstrate that OSCC patients with regional nodal recurrence at unusual sites had poor outcomes.     

Merkel cell carcinoma: a single-centre experience

Background

For patients with merkel cell carcinoma (MCC), the status of regional lymph nodes at presentation is the single most important prognosticating tool, and the procedure is used for managing MCC patients with early stage disease identifying regional nodal micrometastasis.

Methods

A retrospective study was conducted of MCC patients treated at the University Hospital of Aarhus, Denmark, between 1998 and 2013. Outcomes of interest included the time and type of first recurrence after first treatment. In 2010, our institution began using sentinel lymph node biopsy (SLNB) for MCC patients with clinically early stage disease.

Results

Thirty four patients were identified, 61.8 % of the patients presented with stage I disease, 21.5 % with stage II, 11.8 % with stage III and 5.9 % with stage IV. Thirteen patients (38.2 %) had disease recurrence, with local recurrence in three patients, regional recurrence in seven patients and distant recurrence in three patients. Median length of follow-up for all patients was 14.5 months (range 0–86). Since 2010, SLNB has been performed in seven patients; all with negative sentinel lymph nodes (SLN). Three patients had tumour located to the head and neck, three patients to the extremities and one patient to the truncus. Nodal recurrence developed in one of these patients after 5.9 months.

Conclusions

The majority of patients develop recurrence within the first 2 years after initial treatment, most representing with nodal metastasis. The introduction of SLNB may hopefully detect nodal involvement in an early stage, improving the outcome for patients with MCC. Level of Evidence: Level IV, risk/prognostic study.     

Breast Cancer Subtype and Distant Recurrence after Ipsilateral Breast Tumor Recurrence

Background

There is little information about the impact of breast cancer subtype on prognosis after ipsilateral breast tumor recurrence (IBTR).

Methods

One hundred eighty-five patients were classified according to breast cancer subtype, as approximated by estrogen receptor, human epidermal growth factor receptor 2 (HER2), and Ki-67, of IBTR, and we evaluated whether breast cancer subtype was associated with distant recurrence after IBTR.

Results

There was a significant difference in distant disease-free survival (DDFS) after IBTR according to breast cancer subtype defined by a cutoff of the Ki-67 index of 20 % (p = 0.0074, log-rank test). The 5-year DDFS rates for patients with luminal A, luminal B, triple-negative, and HER2 types were 86.3, 57.1, 56.6, and 65.9 %, respectively. In addition, breast cancer subtype was significantly associated with distant recurrence after IBTR on adjustment for various clinicopathologic factors (p = 0.0027, Cox proportional hazards model).

Conclusions

Our study suggests that breast cancer subtype based on immunohistochemical staining predicts the outcomes of patients with IBTR. Further analyses are needed (UMIN-CTR number UMIN000008136).     

Impact of race in a predominantly African-American population of patients with low/intermediate risk prostate cancer undergoing radical prostatectomy within an equal access care institution

Purpose

To study the impact of race in an equal access care institution with a predominantly African-American (AA) population.

Methods

We retrospectively reviewed data from 222 men with low risk (LR) or intermediate risk (IR) prostate cancer who underwent radical prostatectomy at the New York Harbor VA between 2003 and 2011. Biochemical relapse, distant control, and prostate cancer-specific survival were analyzed using the Kaplan–Meier method and compared using the log-rank test. Univariate and multivariate Cox regression modeling was performed to determine the impact of covariates on biochemical outcome.

Results

Most patients (65.3 %) were AA. The median follow-up was 58 months, and 89.6 % of patients were followed for a minimum of 2 years after their surgery. Analyzing the whole cohort, the biochemical control was improved in Caucasian patients compared with AA (90.2 vs. 75.4 %, p = 0.008). On subgroup analysis, for IR disease, this difference was no longer significant, 80.5 % for Caucasians versus 69.8 % for AA (p = 0.36). However, for LR disease, the 5-year biochemical control remained significantly improved for Caucasians compared with AA, with a 5-year biochemical control of 97.6 versus 81.7 %, p = 0.006. On multivariate analysis, AA race was a significant predictor for biochemical recurrence (HR 2.69, 95 % CI 1.27–5.65, p = 0.009). There were no differences between the two groups regarding distant control (p = 0.14) or prostate cancer-specific survival (p = 0.29).

Conclusions

In this predominant AA population with equal access to medical care, AA race is an independent predictor of biochemical recurrence after prostatectomy in men with LR or IR prostate cancer.     

Breast-Conserving Surgery With or Without Radiotherapy in Older Breast Patients With Early Stage Breast Cancer: A Systematic Review and Meta-analysis

Background

In early stage breast cancer, radiotherapy is an integral part of locoregional treatment with breast-conserving surgery. However, few older patients are included in the clinical trials upon which these recommendations are based. Therefore, we performed a systematic review and meta-analysis to evaluate outcomes of radiotherapy after breast-conserving surgery in older patients.

Methods

A systematic search of PubMed and Embase was undertaken. Inclusion was restricted to randomized controlled trials in postmenopausal breast cancer patients. Pooled odds ratios were calculated for locoregional recurrence, distant recurrence, and overall survival.

Results

We included 5 randomized clinical trials comprising 3,190 patients. Overall, 39 % of the patients were ≥70 years old, and most had hormone receptor–positive T1 tumors without nodal involvement. All patients received adjuvant systemic therapy. Patients who received radiotherapy had a lower relative risk of locoregional recurrence (pooled odds ratio [OR] 0.36; 95 % confidence interval [CI] 0.25–0.50). The 5-year absolute risk was 2.2 % (95 % CI 1.6–3.1) among patients who received radiotherapy, versus 6.5 % (95 % CI 5.3–7.9) among patients who did not. The absolute risk difference was 4.3 % (95 % CI 2.9–5.7), corresponding with a number needed to treat of 24. No differences were observed for distant recurrence or overall survival.

Conclusions

Although patients who received radiotherapy had a lower relative risk of locoregional recurrence, the absolute risk was low, and overall survival was not affected. We propose that the debate should not only focus on the relative risk but also on the absolute benefit of radiotherapy and the number needed to treat. Both treatment options may be reasonable in clinical practice.     

Population-Level Analysis of Pancreatic Neuroendocrine Tumors 2 cm or Less in Size

Background

There is a paucity of evidence regarding incidence and predictors of survival in pancreatic neuroendocrine tumors (PNETs) ≤2 cm in size.

Methods

Patients having undergone resection for nonfunctioning PNETs were selected from the SEER database (1988–2009) and an institutional pathology database (1996–2012). PNETs ≤2 cm were compared with PNETs >2 cm. Data were analyzed with χ ² tests, ANOVA, the Kaplan–Meier method, log rank tests, and Cox proportional hazard, and binary logistic regression.

Results

The incidence of PNETs ≤2 cm in the United States has increased by 710.4 % over the last 22 years. Rates of extrapancreatic extension, nodal metastasis, and distant metastasis in PNETs ≤2 cm in the SEER database were 17.9, 27.3, and 9.1 %, respectively. The rate of nodal metastasis in our institutional series was 5.7 %. Disease-specific survival at 5, 10, and 15 years for PNETs ≤2 cm was 91.5, 84.0, and 76.8 %. Decreased disease-specific survival was not associated with nodal metastasis, but rather with high grade [moderately differentiated, hazard ratio (HR) 37.2, 95 % confidence interval (CI) 2.7–518.8; poorly differentiated, HR 94.2, 95 % CI 4.9–1,794.4; reference, well differentiated], and minority race (Asian, HR 30.2, 95 % CI 3.1–291.7; Black, HR 60.1, 95 % CI 2.1–1,027.9; reference, White).

Conclusions

Pancreatic neuroendocrine tumors ≤2 cm are increasingly common, and the most significant predictors of disease-specific survival are grade and race. The SEER database excludes PNETs considered to be benign, and rates of extrapancreatic extension, nodal metastasis, and distant metastasis are overestimated. Small size, however, does not preclude malignant behavior.