Risk Of Locoregional Recurrence In Patients Research Articles

Factors Predicting Locoregional Recurrence After Neoadjuvant Chemotherapy and Nipple-Sparing/Skin-Sparing Mastectomy With Immediate Breast Reconstruction.

BackgroundFew data are available on the risk factors of locoregional recurrence (LRR) after neoadjuvant chemotherapy (NACT) and immediate breast reconstruction (IBR) in breast cancer. Herein, we evaluated the factors predicting LRR in a large series of patients who underwent either nipple- (NSM) or skin-sparing mastectomy (SSM) with IBR after NACT.MethodsWe retrospectively analyzed 609 breast cancer patients who underwent NACT and NSM/SSM with IBR between February 2010 and June 2017. Factors associated with an increased risk of LRR were analyzed by univariate (chi-square or Fisher’s exact test) and multivariate (Cox proportional hazard regression model) analyses.ResultsDuring a median follow-up of 63 months, LRR as the first event occurred in 73 patients, and the 5-year cumulative LRR rate was 10.8%. Multivariate analysis revealed post-NACT Ki67 ≥ 10% [hazard ratio (HR), 2.208; 95% confidence interval (CI), 1.295-3.765; P = 0.004], high tumor grade (HR, 1.738; 95% CI, 1.038-2.908; P = 0.035), and presence of lymphovascular invasion (LVI) (HR, 1.725; 95% CI, 1.039-2.864; P = 0.035) as independently associated with increased LRR risk. The 10-year LRR rate was 8.5% for patients with none of the three associated risk factors, 11.6% with one factor, 25.1% with two factors, and 33.7% with all three factors (P < 0.001).ConclusionsPost-NACT Ki67 ≥ 10%, high tumor grade, and presence of LVI are independently associated with an increased risk of developing LRR after NACT and NSM/SSM with IBR. Future prospective trials are warranted to decrease the risk of LRR in patients with associated risk factors.

Lateral pelvic lymphadenectomy for low rectal cancer: a META-analysis of recurrence rates.

Locoregional recurrence (LR) remains a problem for patients with lower rectal cancer despite standardized surgery and improved neoadjuvant treatment regimens. Lateral pelvic lymph node dissection (LPLND) has been routine practice for some time in the Orient/East, but other regions have concerns about morbidity. As perioperative care and surgical approaches are refined, this has been revisited for selected patients. The question as to whether LPLND improves oncological outcomes was explored here. A systematic review of patients who underwent TME with or without LPLND from 2000 to 2020 was performed. The primary endpoint was the rate of LR between the two groups. Seven papers met the predefined search criteria in which 2000 patients underwent TME alone, while 1563 patients had TME and LPLND. The rate of LR was marginally higher with TME alone when compared with TME plus LPLND, but this result was not statistically significant (9.8 vs 9.4%, odds ratio 0.75, 95% CI 0.41-1.38, *p =0.35). In addition, four studies reported on distant recurrence rates, with TME and LPLND showing a slight reduction in overall rates (27.3 vs 29.9%, respectively, OR 0.65, 95% CI 0.45-0.92, *p =0.02). The addition of LPLND to TME is not associated with a significantly lower risk of LR in patients who undergo surgery for lower rectal cancer.

Association of preoperative breast MRI features with locoregional recurrence after breast conservation therapy.

Background Locoregional recurrence (LRR) following breast conservation therapy (BCT) is associated with an increased risk of distant metastasis and death in patients with breast cancer. Purpose To investigate whether preoperative breast magnetic resonance imaging (MRI) features are associated with the risk of LRR in patients undergoing BCT. Material and Methods A total of 3781 women with primary invasive breast cancer underwent preoperative MRI and BCT between 2003 and 2013. Forty-eight patients who developed LRR comprised the LRR cohort and one-to-one matching (age, tumor stage, grade, and axillary nodal status) of each patient to a control participant was performed in patients who did not develop recurrence. Three readers independently reviewed MR images of the index cancer and the presence of multifocal disease was assessed. Χ2 analysis was used to compare imaging and clinical features between LRR and control cohorts, with multivariate logistic regression analysis used to identify independent features. Results Significant differences were found in the proportion of multifocal disease ( P = 0.001), background parenchymal enhancement level ( P = 0.007), and breast cancer molecular subtype ( P = 0.01) between LRR and control cohorts. Multivariate analysis showed that multifocal disease (odds ratio [OR] = 11.9; 95% confidence interval [CI] = 1.4-102.5; P = 0.02) and human epidermal growth factor receptor 2-positive subtype (OR = 12.7; 95% CI = 1.3-127.6; P = 0.03) were both independently associated with LRR. Conclusion Multifocal disease on preoperative breast MRI may indicate an increased risk of LRR in patients treated with BCT.

Nomogram for Predicting the Risk of Locoregional Recurrence in Patients Treated With Accelerated Partial-Breast Irradiation

To develop a nomogram taking into account clinicopathologic features to predict locoregional recurrence (LRR) in patients treated with accelerated partial-breast irradiation (APBI) for early-stage breast cancer. A total of 2000 breasts (1990 women) were treated with APBI at William Beaumont Hospital (n=551) or on the American Society of Breast Surgeons MammoSite Registry Trial (n=1449). Techniques included multiplanar interstitial catheters (n=98), balloon-based brachytherapy (n=1689), and 3-dimensional conformal radiation therapy (n=213). Clinicopathologic variables were gathered prospectively. A nomogram was formulated utilizing the Cox proportional hazards regression model to predict for LRR. This was validated by generating a bias-corrected index and cross-validated with a concordance index. Median follow-up was 5.5 years (range, 0.9-18.3 years). Of the 2000 cases, 435 were excluded because of missing data. Univariate analysis found that age <50 years, pre-/perimenopausal status, close/positive margins, estrogen receptor negativity, and high grade were associated with a higher frequency of LRR. These 5 independent covariates were used to create adjusted estimates, weighting each on a scale of 0-100. The total score is identified on a points scale to obtain the probability of an LRR over the study period. The model demonstrated good concordance for predicting LRR, with a concordance index of 0.641. The formulation of a practical, easy-to-use nomogram for calculating the risk of LRR in patients undergoing APBI will help guide the appropriate selection of patients for off-protocol utilization of APBI.

Nomogram for predicting the risk of locoregional recurrence in patients treated with accelerated partial-breast irradiation.

59 Background: There are limited tools to guide clinicians regarding the risk of locoregional recurrence (LRR) in patients wishing to pursue APBI. The purpose of this study was to develop a nomogram taking into account clinicopathologic features to predict LRR in patients treated with APBI for early stage breast cancer. Methods: A total of 2,000 breasts (1,990 women) were treated with APBI at William Beaumont Hospital (N=551) or on the ASBrS MammoSite Registry Trial (N=1,449). Techniques included multiplanar interstitial catheters (N=98), balloon-based brachytherapy (N=1,689), and 3D conformal radiotherapy (N=213). Clinicopathologic variables were gathered prospectively. A nomogram was formulated utilizing the Cox Proportional Hazards Regression model to predict for LRR. This was validated by generating a bias-corrected index and cross-validated with a C-index. Results: Median follow-up was 5.5 years (0.9 to 18.3). Of the 2,000 cases, 435 were excluded due to missing data. Univariate analysis found that age &lt;50, pre/perimenopausal status, close/positive margins, ER negativity, and high grade were associated with a higher frequency of LRR. These five independent covariates were used to create adjusted estimates, weighting each on a scale of 0 to 100. The total score is identified on a points scale to obtain the probability of an LRR over the study period. The model demonstrated good concordance for predicting LRR with a C-index of 0.641. Conclusions: The formulation of a practical, easy-to-use nomogram for calculating the risk of LRR in patients undergoing APBI will help guide the appropriate selection of patients for off-protocol utilization of APBI.

Post-mastectomy radiotherapy for breast cancer patients with t1-t2 and 1-3 positive lymph nodes: a meta-analysis.

BackgroundThe role of post-mastectomy radiotherapy (PMRT) in patients with T1-2 and 1-3 positive lymph nodes remains controversial. The aim of this study is to investigate the possible benefits of PMRT for this subgroup.MethodsThree electronic databases were systematically quarried (Cochrane Library, MEDLINE, and EMBASE) for published studies evaluating the effects of PMRT on breast cancer patients with T1-T2 tumors with 1-3 positive lymph nodes. Of the 334 studies identified, information was available for 3432 patients from 10 clinical studies. Pooled relative risk estimates (RR) and overall survival (OS) were calculated using the inverse variance weighted approach, publication bias and chi-square test were also calculated. ResultsFrom the 10 studies, the pooled RR (RRs) for locoregional recurrence (LRR) with PMRT was 0.348 (95% CI = 0.254 to 0.477), suggesting a significant benefit for PMRT to decrease the risk of LRR in patients with T1-T2 tumors and 1-3 positive nodes (p<0.05). Reporting bias ( Begg’s p = 0.152; Egger’s p = 0.107) or significant heterogeneity (Cochran’s p = 0.380; I2 = 6.7%) were not detected. For further subset analysis, the RR for T1, N1-3+ tumors was 0.330 (95% CI = 0.171 to 0.639); for T2, N1-3+ tumors the RR was 0.226 (95% CI = 0.121 to 0.424). The pooled RR for overall survival (OS) was not significantly different between PMRT and no-PMRT group (1.051, 95% CI =1.001 to 1.104).ConclusionsOur pooled analysis revealed that PMRT significantly reduces the risk of LRR in patients with TI-T2 tumors with 1-3 positive nodes, and the magnitude of the LRR risk reduction is slightly greater for larger tumors. Our results suggest that PMRT should be considered for patients with T1/T2 tumors with 1-3 positive nodes to decrease the relatively high risk of LRR.

Prophylactic Supraclavicular Radiotherapy after Surgery in High-Risk N1 Breast Cancer

Objectives: To evaluate the role of prophylactic supraclavicular radiotherapy (RT) by comparing the clinical outcomes of locoregional recurrence (LRR) in high-risk N1 breast cancer. Methods: We performed a retrospective comparison study of 250 high-risk N1 breast cancer patients treated at two institutions. Patients were considered to be high-risk when they had more than two of the following risk factors: lymphovascular invasion, extracapsular extension, metastasis to more than two axillary lymph nodes (ALNs), or level II or higher ALN metastasis. We compared two groups treated with different adjuvant RT fields for the purpose of prophylactic supraclavicular RT (SCRT). Results: Among the 250 patients, 97 patients received SCRT while 153 did not. During follow-up, 32 patients (7 in the SCRT and 25 in the no-SCRT group) had recurrence, and LRR developed in 19 patients, 18 of whom had not received SCRT. In multivariate analysis, SCRT [hazard ratio (HR) 0.072; p = 0.011] and chemotherapy regimen (cyclophosphamide, Adriamycin, and taxane; TAC) were the significant prognostic factors in LRR-free survival (HR 0.385; p = 0.046), and chemotherapy regimen also showed significance for distant metastasis-free survival (HR 0.399; p = 0.037). Conclusions: Use of prophylactic SCRT may reduce the risk of LRR in patients with high-risk N1 breast cancer.

Abstract P3-04-03: A seven-gene profile predicting benefit of postmastectomy radiotherapy independently of nodal status in high risk breast cancer

Abstract Background: Recommendations for postmastectomy radiotherapy (PMRT) are well established in patients estimated to have a high risk of loco-regional recurrence (LR) (e.g. tumor size &amp;gt; 5 cm or ≥ 4 positive lymph nodes). International recommendations for patients with 1–3 positive lymph nodes suggest that PMRT should be restricted to younger patients and patients with other poor prognostic features. However, large randomized trials, including the DBCG82 trials (Danish Breast Cancer Cooperative Group), have previously shown a substantial overall survival benefit after PMRT in patients with low risk of LR, and shown that the largest translation of LR reduction into breast cancer mortality reduction occurs within the most favorable prognosis group. Our hypothesis is that a more refined partitioning of patients likely to benefit from PMRT can be established through identification of genes whose transcription interacts with PMRT to modify the hazard of LR. Material and methods: The DBCG82bc cohort constitutes high risk patients (tumor size &amp;gt; 5 cm and/or positive nodes and/or invasion in skin or pectoral fascia) diagnosed between 1983–89, treated with mastectomy and partial axillary lymph nodes dissection and randomized to +/− PMRT. From 267 DBCG82bc patients, frozen tumor samples were available. Whole genome arrays (Applied Biosystem Human Genome Survey Microarray v2.0®, Applied Biosystem, Foster City, USA) were successful in 195 samples. Genes, whose expression levels interacted with PMRT on the association with LR, were identified through a two step Cox Proportional Hazard model with lasso penalty. 11 node negative patients were excluded from the subsequent analysis of 184 node positive patients (1–3 pos. nodes: 102 pts, ≥ 4 pos. nodes: 82 pts). Results: Seven genes were identified whose expression interact with the effect of PMRT, and a specialized index was generated based on the expression levels of these genes. Patients were ranked according to the size of the index, and divided into quartiles with 25% of the patients designated as having a “high index” and 75% a “low index”. Among patients not receiving PMRT, a low index was in both nodal groups (1–3 vs. ≥ 4 positive nodes) associated with a significantly higher risk of LR compared to patients with a high index. In both nodal groups, PMRT significantly reduced the risk of LR in patients with a low index; equalizing the risk to patients with a high index, who showed no additional LR reduction by PMRT. In the group of 1–3 positive nodes, PMRT raised the local control rate (LCR) after 10 years from 47.5 % to 91.8% in the low index group (p = 0.0001), whereas the change in the high index group was non-significant (92.3% vs. 100.0%). In the group of patients with ≥ 4 positive nodes, PMRT raised LCR from 16.6% to 80.0% in the low index group (p = 0.0001), and no effect on LCR was seen in the high index group (83.3% vs. 87.5%, n.s.). Conclusion: A seven gene-profile attaining prognostic and predictive impact, irrespective of number of positive nodes, was identified. The profile allowed the identification of 25% of the patients not showing any additional benefit from PMRT in terms of LR. The gene-profile may provide a method to identify patients expected to benefit from PMRT. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-04-03.