Independent Risk Factors For Locoregional Recurrence Research Articles

Recurrence Risk Stratification Based on Competing-Risks Nomograms to Identify Patients With Esophageal Cancer Who May Benefit From Postoperative Radiotherapy

A reliable model is needed to estimate the risk of postoperative recurrence and the benefits of postoperative radiotherapy (PORT) in patients with thoracic esophageal squamous cell cancer (TESCC).The study retrospectively reviewed 3652 TESCC patients in stage I-III after radical esophagectomy, with or without PORT. In one institution as the training cohort (n = 1620), independent risk factors associated with locoregional recurrence (LRR), identified by the competing risk regression, were used to establish a predicting nomogram, which was validated in an external cohort (n = 1048). Area under curve (AUC) values of receiver operating characteristic curves were calculated to evaluate discrimination. Risk stratification was conducted using a decision tree analysis based on the cumulative point score of the LRR nomogram, and the effect of PORT was evaluated in each risk group.Sex, age, tumor location, tumor grade, and N category were identified as independent risk factors for LRR and added into the nomogram. The AUC values were 0.638 and 0.706 in the training and validation cohorts, respectively. Three risk groups were established. For patients in the intermediate- and high-risk groups, PORT significantly improved the 5-year overall survival by 8.8% and 11.1%, respectively (P < 0.05). Though PORT was significantly associated with reduced LRR in the low-risk group, overall survival was not improved.The nomogram can effectively estimate the individual risk of LRR, and patients in the intermediate- and high-risk groups are highly recommended to undergo PORT.

Recurrence risk stratification based on a competing-risks nomogram to identify patients with esophageal cancer who may benefit from postoperative radiotherapy.

Background:A reliable model is needed to estimate the risk of postoperative recurrence and the benefits of postoperative radiotherapy (PORT) in patients with thoracic esophageal squamous cell cancer (TESCC).Methods:The study retrospectively reviewed 3652 TESCC patients in stage IB-IVA after radical esophagectomy, with or without PORT. In one institution as the training cohort (n = 1620), independent risk factors associated with locoregional recurrence (LRR), identified by the competing-risks regression, were used to establish a predicting nomogram, which was validated in an external cohort (n = 1048). Area under curve (AUC) values of receiver operating characteristic curves were calculated to evaluate discrimination. Risk stratification was conducted using a decision tree analysis based on the cumulative point score of the LRR nomogram. After balancing the baseline of characteristics between treatment groups by inverse probability of treatment weighting, the effect of PORT was evaluated in each risk group.Results:Sex, age, tumor location, tumor grade, and N category were identified as independent risk factors for LRR and added into the nomogram. The AUC values were 0.638 and 0.706 in the training and validation cohorts, respectively. Three risk groups were established. For patients in the intermediate- and high-risk groups, PORT significantly improved the 5-year overall survival by 10.2% and 9.4%, respectively (p < 0.05). Although PORT was significantly associated with reduced LRR in the low-risk group, overall survival was not improved.Conclusion:The nomogram can effectively estimate the individual risk of LRR, and patients in the intermediate- and high-risk groups are highly recommended to undergo PORT.

Risk stratification for prediction of locoregional recurrence in patients with pathologic T1\u20132N0 breast cancer after mastectomy

BackgroundPrevious studies have revealed that nearly 15–20% of selected high-risk T1–2N0 breast cancers developed LRR after mastectomy. This study is aim to indentify the risk factors of locoregional recurrence (LRR) in patients with pathologic T1–2N0 breast cancer after mastectomy in a real-world and distinguish individuals who warrant postmastectomy radiotherapy (PMRT).MethodsFemale patients treated from 1999 to 2014 in National Cancer Center of China were retrospectively reviewed. A competing risk model was developed to estimate the cumulative incidence of LRR with death treated as a competing event.ResultsA total of 4841 patients were eligible. All underwent mastectomy plus axillary nodes dissection or sentinel node biopsy without PMRT. With a median follow-up of 56.4 months (range, 1–222 months), the 5-year LRR rate was 3.9%.Besides treatment era, age ≤ 40 years old (p < 0.001, hazard ratio [HR] = 2.262), tumor located in inner quadrant (p < 0.001, HR = 2.236), T2 stage (p = 0.020, HR = 1.419), and negative expressions of estrogen receptor (ER) and progesterone receptor (PR) (p = 0.032, HR = 1.485), were patients-related independent risk factors for LRR. The 5-year LRR rates were 1.7, 3.5, and 15.0% for patients with zero, 1–2, and 3–4 risk factors (p < 0.001).ConclusionsRisk Stratification based on age, T stage, ER/PR status and tumor location can stratify patients with pT1–2 N0 breast cancer into subgroups with different risk of LRR. PMRT might be suggested for patients with 3–4 risk factors.

Oncologic Outcomes of Nipple-sparing Mastectomy and Immediate Reconstruction After Neoadjuvant Chemotherapy for Breast Cancer.

To evaluate the oncologic outcomes and risk factors for locoregional recurrence (LRR) and nipple-areola complex recurrence (NR) in a large series of breast cancer patients who underwent nipple-sparing mastectomy (NSM) and immediate reconstruction after neoadjuvant chemotherapy (NACT). The use of NSM and immediate reconstruction in breast cancer patients receiving NACT is increasing. However, the oncologic safety of this approach is unclear. A total of 310 breast cancer patients (319 breasts) who underwent NACT and NSM between February 2010 and November 2016 were retrospectively analyzed. Clinical and pathologic factors associated with increased risks of LRR and NR were analyzed using univariate (Chi-square or Fisher exact test) and multivariate (Cox proportional hazard regression model) analyses. During a mean follow-up of 63 ± 22 months, 38 cases had LRR as the first event, including 6 cases of NR as the first event. The 5-year cumulative LRR and NR rates were 11.0% and 1.9%, respectively. In univariate analysis, clinical T stage, pathologic nodal status, histologic grade, lymphovascular invasion, and post-NACT Ki67 status were associated with increased LRR risk, and post-NACT Ki67 status was the only significant risk factor for NR. In multivariate analysis, post-NACT Ki67 ≥10% (hazard ratio, 4.245; 95% confidence interval, 1.865-9.663; P = 0.001) was an independent risk factor for LRR. NSM and immediate reconstruction seem to be oncologically safe with acceptable LRR and NR rates for appropriately selected breast cancer patients treated with NACT. Post-NACT Ki67 ≥10% was associated with increased risk of LRR or NR, and therefore, necessitates cautious follow-up.

Recurrence Outcomes After Nipple-Sparing Mastectomy and Immediate Breast Reconstruction in Patients with Pure Ductal Carcinoma In Situ.

Nipple-sparing mastectomy (NSM) has become increasingly prevalent for patients with ductal carcinoma in situ (DCIS) requiring mastectomy. However, few data regarding recurrence outcomes after NSM are available for this patient population. This study evaluated the locoregional recurrence (LRR) rate for patients with pure DCIS who underwent NSM followed by immediate breast reconstruction without adjuvant radiotherapy and investigated potential risk factors for LRR and/or nipple-areola complex recurrence (NR). A retrospective chart review was performed for 199 consecutive patients with pure DCIS who underwent NSM and immediate breast reconstruction between March 2003 and December 2015. Risk factors for LRR and NR were analyzed using univariate (Chi square test) and multivariate (Cox model) methods. The median follow-up duration after surgery was 97months (range, 39-186months). At 10years, the LRR rate was 4.5%, and the NR rate was 3%. The univariate analysis showed that high nuclear grade, negative receptor status, positive human epidermal growth factor receptor 2 (HER2) status, and negative hormone receptor/positive HER2 subtype were associated with increased risk for NR. The multivariate analysis demonstrated that negative progesterone receptor status was an independent risk factor for LRR. However, margin status and tumor-to-nipple distance (TND) were not associated with increased risk for either LRR or NR. The study findings suggest that NSM can be a feasible surgical option even for DCIS with a TND of 1cm or less if the retroareolar resection margin is negative for malignancy. Determining the molecular subtype of DCIS might be helpful in identifying patients at high risk for recurrence.

Risk Prediction for Locoregional Recurrence in Epidermal Growth Factor Receptor-Mutant Stage III-pN2 Lung Adenocarcinoma after Complete Resection: A Multi-center Retrospective Study

Background: This study aimed to develop a predictive model based on the risk of locoregional recurrence (LRR) in epidermal growth factor receptor (EGFR)-mutant stage III-pN2 lung adenocarcinoma after complete resection.Methods: A total of 11,020 patients with lung surgery were screened to determine completely resected EGFR-mutant stage III-pN2 lung adenocarcinoma. Patients were excluded if they received preoperative therapy or postoperative radiation therapy (PORT). The time from surgery to LRR was recorded. Clinicopathological variables with statistical significance predicting LRR in the multivariate Cox regression were incorporated into the competing risk nomogram. Patients were then sub-grouped based on different recurrence risk as a result of the nomogram.Results: Two hundred and eighty-eight patients were enrolled, including 191 (66.3%) with unforeseen N2 (IIIA1-2), 75 (26.0%) with minimal/single station N2 (IIIA3), and 22 (7.6%) with bulky and/or multilevel N2 (IIIA4). The 2-year overall cumulative incidence of LRR was 27.2% (confidence interval [CI], 16.3%-38.0%). IIIA4 disease (hazard ratio, 2.65; CI, 1.15-6.07; P=0.022) and extranodal extension (hazard ratio, 3.33; CI, 1.76-6.30; P<0.001) were independent risk factors for LRR and were incorporated into the nomogram. Based on the nomogram, patients who did not have any risk factor (low-risk) had a significantly lower predicted 2-year incidence of LRR than those with any of the risk factors (high-risk; 4.6% vs 21.9%, P<0.001).Conclusions: Pre-treatment bulky/multilevel N2 and pathological extranodal extension are risk factors for locoregional recurrence in EGFR-mutant stage III-pN2 lung adenocarcinoma. Intensive adjuvant therapies and active follow-up should be considered in patients with any of the risk factors.

Pretreatment clinical stage predicts locoregional recurrence in patients with esophageal cancer who achieved a complete clinical response to chemoradiotherapy

ObjectiveDefinitive chemoradiotherapy (dCRT) represents a curative nonsurgical treatment option for patients with esophageal cancer. However, tumor recurrence is common after dCRT, even when clinical complete response (cCR) is achieved. Here, we investigated the timing, patterns, and risk factors for recurrence in patients with esophageal squamous cell carcinoma (ESCC) who achieved cCR following dCRT. MethodsWe retrospectively examined the clinical records of patients with ESCC who achieved cCR following dCRT between 2001 and 2014. Locoregional recurrence (LR) was defined as a recurrence occurring in the esophageal lumen and/or locoregional lymph nodes. Recurrences at any other sites were considered as distant recurrences (DRs). ResultsA total of 102 patients who achieved cCR were included. After a mean follow-up of 54.5 months, 51 patients developed recurrences (34 LRs, 6 combined LR and DR, and 11 DRs). The cumulative 1-, 3-, and 5-year recurrence rates were 35%, 46%, and 50%, respectively. The mean time to recurrence for the 40 patients with LRs (including LRs plus LRs/DRs) was significantly shorter (281.4 days) compared with that of patients with DRs (643.6 days; P = .006), with 95% of the former being diagnosed within 2 years. Multivariate Cox regression analysis identified pretreatment clinical stage III as the only independent risk factor for LR (hazard ratio, 2.732; 95% confidence interval; 1.063-7.020; P = .037). ConclusionsDisease recurrence occurs in 50% of ESCC patients who achieve cCR following dCRT, with LR being the most common pattern. Advanced pretreatment clinical stage is an independent risk factor for LR.

Possible benefits from post-mastectomy radiotherapy in node-negative breast cancer patients: a multicenter analysis in Korea (KROG 14-22).

PurposeThis study was performed to identify a subset of patients who may benefit from post-mastectomy radiotherapy (PMRT) among node-negative breast cancer patients.Materials and MethodsWe retrospectively reviewed 1,828 patients with pT1-2N0 breast cancer, treated with mastectomy without PMRT from 2005 to 2010 at 10 institutions. Univariate and multivariate analyses for locoregional recurrence (LRR) and any first recurrence (AFR) were performed according to clinicopathologic factors and biologic subtypes.ResultsDuring a median follow-up period of 5.9 years (range: 0.7-10.4 years), 98 patients developed AFR (39 isolated LRR, 13 LRR with synchronous distant metastasis, and 46 isolated distant metastasis), and 52 patients developed LRR. The 7-year LRR and AFR rates were 3.8% and 6.7%, respectively. Multivariate analysis revealed that age of ≤ 40 years (p<0.001) and T2 stage (p=0.013) were independent risk factors for LRR. The 7-year LRR rates were 2.5% with no risk factors, 4.5% with one risk factor, and 12.4% with two risk factors. Multivariate analysis for AFR revealed that age of ≤ 40 years (p<0.001), T2 stage (p<0.001), and triple-negative biological subtype (p=0.045) were independent risk factors for AFR. The 7-year AFR rates were 3.9% with no risk factors, 8.4% with one risk factor, and 15.7% with two to three risk factors.ConclusionsMastectomy without PMRT is a sufficient local treatment for pT1-2N0M0 breast cancer. Nevertheless, PMRT might be considered for patients with two or three risk factors, among those of young age, with T2 tumors, and with the triple-negative biological subtype based on LRR and AFR.

Predictive Value of Primary Tumor Site for Loco-regional Recurrence in Early Breast Cancer Patients with One to Three Positive Axillary Lymphadenophy.

Introduction: It remains controversial on high risks for early breast cancer patients with one to three axillary nodes after mastectomy who is predisposition to locoregional recurrence. The present study is to investigate the relationship between primary tumor site and loco-regional recurrence (LRR) and explore the predictive value of clinicopathological characteristics in LRR for early breast cancer patients with one to three positive axillary lymph nodes after mastectomy.Methods: We reviewed the clinical data of 656 consecutively diagnosed patients with pT1-2N1M0 breast cancer who were treated in Sun Yat-sen University Cancer Center with radical operation without postoperative radiotherapy between March 1998 and December 2010. The primary tumor sites included outer quadrant in 455 patients (69.36%), inner quadrant in 156 patients (23.78%)and central quadrant in 45 patients (6.86%). LRR and LRR-free survival (LRFS) in combination with clinical and pathological features were analyzed to screen out patients with higher risk of LRR.Results: The median follow-up time was 64.9 months. The 5-, 10-year LRR for the cohort was 8.6% and 12.9%, respectively; the 5-, 10-year LRFS was 86.2% and 76.4%, respectively. Multivariate analyses showed that age of ≤35 years, inner quadrant tumor and non-luminal subtype were independent risk factors for LRR and LRFS. Patients with primary tumor in inner quadrant showed higher LRR and poorer LRFS when risk factors are ≥2 than those with tumors in other sites.Conclusions: Inner quadrant tumor was an independent predictor for LRR and LRFS in patients with early breast cancer and one to three positive axillary lymph nodes, which would be more accurate in combination with other prognostic indexes including patients' age, pathological T stage, Ki67 status, molecular subtypes.

Identification of Risk Factors for Locoregional Recurrence in Breast Cancer Patients with Nodal Stage N0 and N1: Who Could Benefit from Post-Mastectomy Radiotherapy?

IntroductionThe locoregional recurrence (LRR) rate was reported as high as approximately 20% in stage I-II breast cancer following mastectomy. To investigate the risk factors for LRR in pT1–2N0-1 breast cancer patients treated with mastectomy but not radiation, and to define a subgroup of patients at high risk of LRR who may benefit from postmastectomy radiotherapy (PMRT).Methods and MaterialsIn total, 390 patients with pT1-2N0M0 (n = 307) and pT1-2N1M0 (n = 83) breast cancer who underwent total mastectomy without adjuvant radiotherapy from 2002 to 2011 were enrolled in the study.ResultsAfter a median follow-up period of 5.6 years (range, 0.6–11.3 years), 21 patients had 18 systemic relapses and 12 LRRs including six in the chest wall and eight in the regional nodal area. The 5-year LRR-free survival (LRRFS) rates were 97.0% in pN0, 98.8% in pN1, and 97.4% in all patients. Multivariate analysis revealed that age < 50 years (Hazard Ratio, 11.4; p = 0.01) and no adjuvant chemotherapy (Hazard Ratio, 10.2; p = 0.04) were independent risk factors for LRR in pN0 patients. Using these factors, the 5-year LRRFS rates were 100% without any risk factors, 96.4% with one risk factor, and 86.7% with two risk factors. In pN1 patients, multivariate analysis revealed that having a hormone receptor negative tumor (Hazard Ratio, 18.3; p = 0.03) was the only independent risk factor for LRR. The 5-year LRRFS rates were 100.0% for luminal type, and 92.3% for non-luminal type cancer.ConclusionPatients with pT1-2N0-1 breast cancer who underwent total mastectomy without PMRT could be stratified by nodal stage and risk factors for LRR. PMRT may have of value for node negative patients aged less than 50 years and who are not treated with adjuvant chemotherapy, and for non-luminal type patients with one to three positive nodes.

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

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. 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. 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). 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.

Locoregional recurrence risk factors and the impact of postmastectomy radiotherapy on patients with tumors 5 cm or larger

Locoregional recurrence (LRR) after mastectomy reduces the patient's quality of life and survival. There is a consensus that postmastectomy radiotherapy (PMRT) helps achieve locoregional control and reduces LRR. However, in patients with large tumors, the question of which variables affect the likelihood of LRR and the role of PMRT have been subjects of substantial controversy. This study investigated what the risk factors are for LRR and the efficacy of PMRT in this patient population. This retrospective study examined 589 cases of invasive breast carcinoma with tumors 5cm or larger from 1998 to 2008. We divided the study population into 3 groups: patients with negative nodes, 1-3 positive nodes, and ≥4 positive nodes. The relationship between various clinicopathological variables and LRR was examined, and the relationship between LRR and PMRT was estimated. During the median follow-up of 44.2months, 38 (6.5%) patients experienced LRR. In the multivariate analysis, independent risk factors for LRR included pectoral invasion in patients with 1-3 positive nodes, severity of lymphatic invasion, estrogen receptor-negative status, and a nodal ratio of positive/excised nodes >0.50 in patients with ≥4 positive nodes. In patients without positive nodes, none of the examined variables were significantly associated with LRR. Although patients treated with PMRT had good outcomes, there was no significant difference. With systemic therapy and adequate lymph node dissection, PMRT by itself was of limited value in establishing locoregional control. Due to the very low incidence of LRR observed, PMRT was not necessary for patients with large tumors without lymph node metastasis. Further examination and consensus about the indications for PMRT in patients with 1-3 metastatic nodes are needed.

Locoregional recurrence in breast carcinoma patients

Aims To assess the risk of locoregional recurrence (LRR) after mastectomy and to identify predictive and treatment factors that affect the risk of LRR. Methods The primary endpoint was local recurrence. Univariate and multivariate Cox regression analyses were carried out in the data from 1217 patients. Results The median follow-up was 74 months, and 63 (5.2%) patients experienced a LRR in their follow-up period. In the multivariate analysis, age group (≤35 years vs. >35 years, p < 0.0001; Hazard Ratio [HR], 5.0; 95% Confidence Interval [95% CI], 3.0–8.3), tumour size (>2 cm vs. ≤2 cm, p = 0.03; HR, 2.2; 95% CI, 1.2–4.7) and LVI (yes vs. no, p < 0.0001; HR, 3.2; 95% CI,1.9–5.2) were the independent prognostic factors for LRR. This analysis, in the final model, indicated that adjuvant radiotherapy and adjuvant tamoxifen were associated with a reduced risk of LRR by 90% and 75%, respectively, across the follow-up period, whereas age group remained as an important risk factor ( p = 0.002; HR, 3.0; 95% CI, 1.5–6.2). Conclusions Although adjuvant therapies reduce the risk of LRR, young age is an independent risk factor for LRR.