Validation of a prognostic scoring system for postmastectomy locoregional recurrence in breast cancer

BackgroundTo date, it remains unclear which patients with breast cancer (BC) benefit from post-mastectomy radiotherapy (PMRT). Cheng et al. developed and validated a scoring system based on 4 prognostic factors for locoregional recurrence (LRR) to identify patients in need for PMRT. These factors include age, estrogen receptor status, lymphovascular status and number of affected axillary lymph nodes.PurposeTo validate the scoring system for LRR in BC developed by Cheng et al. by using an independent BC database.Methods and materialsWe retrospectively identified 1989 BC cases, treated with mastectomy (ME) with or without PMRT at the University Hospitals Leuven between 2000 and 2007. The primary endpoint was 5-year locoregional control rate with and without PMRT, according to the LRR score.ResultsMedian follow-up time was 11.4 years. After excluding patients with missing variables 1103 patients were classified using the LRR scoring system: 688 (62.38%) patients were at low risk of recurrence (LRR score 0–1), 335 (30.37%) patients were at intermediate risk of recurrence (LRR score 2–3) and 80 (7.25%) patients were at high risk of recurrence (LRR score ≥4). 5-year locoregional control rates with and without PMRT were 99.20% versus 99.21% (p = 0.43) in the low-risk group; 98.24% versus 85.74% (p < 0.0001) in the intermediate-risk group and 96.87% versus 85.71% (p = 0.10) in the high-risk group respectively.ConclusionOur validation of the LRR scoring system suggests it can be used to point out patients that would benefit from PMRT. We recommend further validation of this scoring system by other independent institutions before application in clinical practice.     

Postmastectomy radiation therapy and survival outcome in older patients with T1-2N1 breast cancer

BackgroundThe prognostic impact of postmastectomy radiation therapy (PMRT) on contemporary older patients with T1-2N1 breast cancer is unclear. We aimed to investigate the effect of PMRT in this setting.MethodsLeveraging the Surveillance, Epidemiology, and End Results (SEER) program data from 2004 to 2015, 7052 patients aged 70 years or older with T1-2N1 breast cancer were identified for this propensity-matched analysis. Fine and Gray competing risks regression was conducted to explore the correlation between PMRT and breast cancer-specific survival, in subgroups defined by tumor size and positive lymph nodes.ResultsThe median follow-up was 60.1 months (interquartile range, 28.0 to 87.0). Among propensity-matched patients, multivariate analysis identified an association between PMRT and decreased breast cancer mortality (BCM; HR 0.637; 95 % CI 0.436–0.931; P = 0.020) in patient subset with three positive nodes and tumors 2–5 cm in size, and this benefit was limited to patients with three positive nodes and tumors 2–5 cm in size who did not receive chemotherapy. In patient subsets who received chemotherapy, no association between PMRT and BCM was found.ConclusionPMRT was not associated with BCM in older patients with T1-2N1 breast cancer who received chemotherapy. The benefit of PMRT was limited to those with three positive nodes and tumors 2–5 cm in size who did not receive chemotherapy.     

Suggestion for the omission of post-mastectomy chest wall radiation therapy in patients who underwent skin-sparing/nipple-sparing mastectomy

AimBoth skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) have been widely adopted. Although postmastectomy radiation therapy (PMRT) can improve clinical outcomes, it can worsen cosmesis following reconstruction. Therefore, identifying risk factors of ipsilateral breast tumor recurrence (IBTR) could help de-escalate PMRT after NSM/SSM in patients with pT1-2 disease.MethodsWe retrospectively reviewed patients treated with SSM (N = 400) and NSM (N = 156) in patients with pT1-2N0-1 disease between 2009 and 2016. Seventy-four patients received PMRT with 50–50.4 Gy in 25–28 fractions. The Cox proportional hazards model was used to analyze the prognostic factors of IBTR.ResultsWith a median follow-up of 66.2 months, 17 IBTR events were observed, with 5-year IBTR-free rate of 97.2%. Although only one IBTR was observed after PMRT, there was no statistical difference in the 5-year IBTR-free rate (PMRT vs. no PMRT, 98.6% vs. 97.0%, p = 0.360). Multivariable analyses demonstrated that age ≤45 years and lymphovascular invasion (LVI) were adverse features of IBTR. The low-risk group (0 risk factor) showed a better 5-year IBTR-free rate than the high-risk group (≥1 risk factor) (100.0% vs. 95.8%, p = 0.003). In the high-risk group, PMRT slightly improved 5-year IBTR-free rate compared with no PMRT (98.6% vs. 95.2%, p = 0.166). In addition, PMRT increased 5-year cumulative incidence of reconstruction failure (10.0% vs. 2.8%, p = 0.001).ConclusionWe identified risk factors (age and LVI) related to IBTR following upfront SSM/NSM with pT1-2 disease. As a hypothesis-generating study, de-escalation of PMRT by omitting chest wall irradiation in selective patients could improve reconstruction-related complications without compromising oncologic outcomes.     

Effect of postmastectomy radiotherapy on pT1-2N1 breast cancer patients with different molecular subtypes

ObjectiveTo clarify the effect of postmastectomy radiotherapy (PMRT) on pT_1-2N₁ breast cancer patients with different molecular subtypes.MethodsWe retrospectively analyzed the data of 5442 patients with pT_1-2N₁ breast cancer treated using modified radical mastectomy in 11 hospitals in China. Univariate, multivariate, and propensity score matching (PSM) analyses were used to evaluate the effect of PMRT on locoregional recurrence (LRR).ResultsWith a median follow-up duration of 63.8 months, the 5-year LRR rates were 4.0% and 7.7% among patients treated with and without PMRT, respectively (p < 0.001). PMRT was independently associated with reduced LRR after adjustments for confounders (p < 0.001). After grouping the patients according to the molecular subtype of cancer and conducting PSM, we found that the 5-year LRR rates among patients treated with and without PMRT (in that order) were as follows: luminal HER2-negative cancer, 1.9% and 6.5% (p < 0.001); luminal HER2-positive cancer, 3.8% and 13.7% (p = 0.041); HER2-overexpressing cancer, 10.2% and 15.5% (p = 0.236); and triple-negative cancer, 4.6% and 15.9% (p = 0.002). Among patients with HER2-overexpressing and triple-negative cancers, the LRR hazard rate displayed a dominant early peak, and was extremely low after 5 years. However, patients with luminal cancer continued to have a long-lasting high annual LRR hazard rate during follow-up.ConclusionPMRT significantly reduced the LRR risk in patients with pT_1-2N₁ luminal and triple-negative breast cancers, but had no effect on the LRR risk in patients with HER2-overexpressing cancer. Patients with different molecular subtypes displayed different annual LRR patterns, and the late recurrence of the luminal subtype suggests the necessity of long-term follow-up to evaluate the efficacy of PMRT.     

Present-Day Locoregional Control in Patients with T1 or T2 Breast Cancer with 0 and 1 to 3 Positive Lymph Nodes After Mastectomy Without Radiotherapy

Background

We sought to determine present-day locoregional recurrence (LRR) rates to better understand the role of postmastectomy radiotherapy (PMRT) in women with 0 to 3 positive lymph nodes.

Methods

Clinical and pathologic factors were identified for 1019 patients with pT1 or pT2 tumors and 0 (n = 753), 1 (n = 176), 2 (n = 69), or 3 (n = 21) positive lymph nodes treated with mastectomy without PMRT during 1997 to 2002. Total LRR rates were calculated by Kaplan-Meier analysis and compared between subgroups by the log rank test.

Results

After a median follow-up of 7.47 years, the overall 10-year LRR rate was 2.7%. The only independent predictor of LRR was younger age (P = 0.004). Patients ≤40 years old had a 10-year LRR rate of 11.3 vs. 1.5% for older patients (P < 0.0001). The 10-year rate of LRR in patients with 1 to 3 positive nodes was 4.3% (94.4% had systemic therapy), which was not significantly different from the 10-year risk of contralateral breast cancer development (6.5%; P > 0.5). Compared with the 10-year LRR rate among patients with node-negative disease (2.1%), patients with 1 positive node had a similar 10-year LRR risk (3.3%; P > 0.5), and patients with 2 positive nodes had a 10-year LRR risk of 7.9% (P = 0.0003). Patients with T2 tumors with 1 to 3 positive nodes had a 10-year LRR rate of 9.7%.

Conclusions

In patients with T1 and T2 breast cancer with 0 to 3 positive nodes, LRR rates after mastectomy are low, with the exception of patients ≤40 years old. The indications for PMRT in patients treated in the current era should be reexamined.     

Influence of age as a continuous variable on the prognosis of patients with pT1-2N1 breast cancer

PurposeTo assess the influence of age as a continuous variable on the prognosis of pT1-2N1 breast cancer and examine its decision-making value for postmastectomy radiotherapy (PMRT).MethodsWe retrospectively evaluated 5438 patients with pT1-2N1 breast cancer after mastectomy in 11 hospitals. A multivariable Cox proportional hazards regression model with penalized splines was used to examine the relationship between age and oncologic outcomes.ResultsThe median follow-up was 67.0 months. After adjustments for confounding characteristics, nonsignificant downward trend in locoregional recurrence (LRR) risk was observed with increasing age (P-non-linear association = 0.640; P-linear association = 0.078). A significant non-linear association was found between age and disease-free survival (DFS) and overall survival (OS) (P-non-linear association <0.05; P-linear association >0.05, respectively). The DFS and OS exhibited U-shaped relationships, with the hazard ratios (HRs), reaching a nadir at 50 years old. A decreased risk of LRR with PMRT vs. no PMRT (HR = 0.304, 95% CI: 0.204–0.454) was maintained in all ages. The HR of PMRT vs. no PMRT for DFS and OS gradually increased with age. In patients ≤50 years old, PMRT was independently associated with favorable LRR, DFS, and OS, all P < 0.05). In patients >50 years old, PMRT was independently associated with reduced LRR (P = 0.004), but had no effect on DFS or OS.ConclusionsAge was an independent prognostic factor for pT1-2N1 breast cancer; PMRT provided survival benefits for patients ≤50 years old, but not for patients >50 years old.     

The survival benefit of postmastectomy radiotherapy for breast cancer patients with T1-2N1 disease according to molecular subtype

ObjectiveTo evaluate the significance of postmastectomy radiotherapy (PMRT) in female breast cancer patients with T1-2N1M0 disease according to molecular subtypes and other risk factors.MethodWe conducted a retrospective cohort-based study utilizing the Surveillance, Epidemiology, and End Results database. Patients who were diagnosed with T1-2N1M0 invasive breast cancer and received mastectomy between 2010 and 2014 were enrolled in our study. Overall survival (OS) was calculated with Kaplan-Meier method, and multivariant Cox hazard model was conducted to identify the impact of PMRT according to molecular subtypes and other risk factors. Propensity score matching (PSM) was applied to balance measurable confounders.ResultsOf all the 16,521 enrolled patients, 5775 (35.0%) cases received PMRT. The distribution of molecular subtype is 71.4% for Luminal A, 13.2% for Luminal B, 5.1% for HER2 enriched, and 10.3% for TNBC. The OS was significantly better for patients in PMRT group than the Non-PMRT group (P < 0.0001). Stratified by molecular subtype, PMRT significantly prolonged survival in Luminal A patients (HR: 0.759, 95% CI: 0.651–0.884, P < 0.001), Yet it brought no significant survival advantage in Luminal B, TNBC or HER2 enriched subtype (P = 0.914, P = 0.124, P = 0.103, respectively). Also, PMRT bore prognostic significance among those patients who were older than 56 years old, single, white, exempt from reconstruction and chemotherapy, and were with ductal, GradeⅡtumor (all P < 0.05). After PSM, the survival benefit of PRMT sustained in Luminal A patients with T1 tumor concomitant with one positive lymph node.ConclusionOur study demonstrates a beneficial impact for PMRT on overall survival among Luminal A subtype breast cancer patients with T1-2N1 disease. The selection of PMRT should be stratified by molecular subtype and other risk factors.     

Clinical characteristics and survival outcome of patients with estrogen receptor low positive breast cancer

BackgroundThe benefit of endocrine therapy for patients with estrogen receptor (ER)-low (1%–10%) positive breast cancer is a matter for debate. We aimed to compare the clinical characteristics and survival outcome of ER-low patients with ER-high (＞10%) positive patients and ER-negative patients.MethodsFrom the breast cancer database of our institution, we identified 5466 patients with known ER status who were diagnosed with early-stage breast cancer between January 2008 and December 2016. Variables associated with initiation of endocrine therapy were identified using multivariate logistic regression model. According to ER status, all patients were classified into ER-low (1%–10%), ER-high (>10%) and ER-negative subgroups. Fine and Gray competing risks regression was performed to compare the survival outcome of three subgroups.ResultsAge at diagnosis, ER status and progesterone receptor (PR) status were identified as correlates of initiation of endocrine therapy. ER-low patients were more likely to have advanced, PR-negative, human epidermal growth factor receptor 2 (HER2)-positive or grade Ⅲ disease compared to ER-high patients. Similar to ER-negative patients, ER-low patients presented increased rate of locoregional recurrence (LRR), distant recurrence (DR) and breast cancer mortality (BCM) than ER-high patients. Endocrine therapy showed nonsignificant trends toward lower LRR, DR and BCM in ER-low patients.ConclusionSimilar to ER-negative patients, ER-low patients had more aggressive clinical characteristics and worse survival outcome than ER-high patients. ER-low patients appeared to benefit less from endocrine therapy. Randomized studies are needed to further explore the endocrine responsiveness of ER-low patients.     

Effects of postmastectomy radiotherapy on survival in different age groups for patients with T3N0M0 breast cancer

BackgroundPostmastectomy radiotherapy (PMRT), as an important regional treatment, improves the survival rate of patients with T3N0M0 breast cancers. However, the therapeutic effect of PMRT on T3N0M0 patients in different age groups is unclear.MethodsUsing Surveillance, Epidemiology, and End Results database, we identified 4840 T3N0M0 patients between 2000 and 2015. The primary and secondary outcomes were overall survival (OS) and breast cancer-specific survival (BCSS). Survival outcomes were compared using Kaplan-Meier survival test, COX regression analysis, propensity score matching and forest plot, which present the relationship between age and PMRT.ResultsSurvival analysis demonstrated that for young patients (aged 18–45 and 46–55), there was no significant difference in OS between with and without PMRT. However, for patients older than 65 years, PMRT could significantly improve survival time (P < 0.001). Multivariate Cox analysis of OS showed older patients with PMRT had a lower hazard ratio (HR) than those without PMRT (aged 56–65: HR = 0.67, P = 0.014; aged >65: HR = 0.60, P < 0.001), and little benefit for young patients. The consistent results were also observed in 1:1 matched cohort. Subgroup analysis revealed the survival HRs of with versus without PMRT for patients older than 65 years were significant in most subgroups.ConclusionThe effect of PMRT in T3N0M0 patients is related to the age. PMRT is associated with improved survival in older patients with T3N0M0 breast cancer, especially those older than 65 years. While the benefit of PMRT is limited in T3N0M0 patients of young age. The observation suggests the importance of age for T3N0M0 patients when individualized treatment is made.     

The prognostic significance of Gail model risk factors for women with breast cancer

BACKGROUND: Because many risk factors for breast cancer are related to hormonal factors and hormonal factors influence breast cancer prognosis, risk factors may have prognostic value. In order to assess the prognostic value of risk factors for breast cancer we divided patients with breast cancer into those at high risk and low risk using the Gail model. METHODS: Patients with available follow-up and information concerning age, age at menarche, number of children, age at first birth, number of first degree relatives with breast cancer, and number of previous breast biopsies were divided into low and high-risk groups by the average relative risk calculated using the Gail model. Risk factors, clinical presentations, pathologic findings, tumor characteristics, extent of disease, treatment and outcomes for the 106 high-risk women were compared with the 206 low-risk women. Stage IV patients were excluded. RESULTS: The average relative risk of breast cancer was 2.09. The 106 high-risk women were significantly older (58 years versus 53 years; P = 0.001), older at first live birth (30 years versus 23 years; P <0.001), more likely to have a first degree relative with breast cancer (57% versus 0%; P <0.001), and more likely to have previously had a breast biopsy (19% versus 1%; P <0.001). There was no difference in the average age at menarche. Low-risk patients were significantly more frequently nulliparous (40% versus 22%; P = 0.002). Clinical presentation, pathologic findings, extent of disease, and treatment were comparable in high and low-risk patients. Cancers of low-risk patients were more frequently poorly differentiated (39% versus 25%, P = 0.044). Tamoxifen was used more frequently in high-risk patients (56% versus 41%; P = 0.012). High-risk patients exhibited significantly better 5-year (95% versus 88%; P = 0.047) and 10-year distant disease-free survival than low-risk patients (88% versus 79%; P = 0.050). In multivariate analysis only the number of involved lymph nodes was related to local (P = 0.001) and distant (P <0.001) disease-free survival. CONCLUSIONS: Breast cancer patients considered high risk by the Gail model have significantly better disease-free survival than low-risk patients. This study does not support the notion that risk factors for breast cancer are prognostic factors.     

Low risk of recurrence in elderly patients treated with breast conserving therapy in a single institute

ObjectivesTo guide decision making in preventing over- or under-treatment in older breast cancer patients who have undergone breast conserving surgery, we analyzed prognostic factors and risk of recurrence in a consecutive series of patients ≥ 65 years old with breast cancer and identified subgroups that may benefit or not from more intensive treatment.MethodsPatients ≥65 years of age with breast cancer (pT1-2/pN0-2) treated with breast conserving surgery and postoperative radiation therapy at the Netherlands Cancer Institute (NKI) between 1980 and 2008 were identified. Endpoints were locoregional recurrence (LRR), distant metastasis (DM) and overall survival (OS). Multivariable analyses were performed using Cox proportional hazards models.Results1922 patients with a median age of 70 years were analyzed. The 5- and 10- years LRR rates were 2% and 3% respectively. In multivariable analysis there was no significant factor influencing LRR risk. Patients with low risk tumors (node negative patients with T1 and ER positive, grade 1 or 2) had lower risk of DM (HR 0.26) and better OS (HR 0.65) compared to patients with higher risk tumors (grade 3 and/or node positive).ConclusionIn elderly breast cancer patients the risk of LRR and DM is low. In patients with less favorable characteristics the risk of LRR is equally low, with a higher risk to develop DM and worse OS. Treatment in the low risk group may be minimized, while for the higher risk group adjuvant treatment could be intensified.     

Outcomes and utilization of postmastectomy radiotherapy for T3N0 breast cancers

BackgroundThe role of postmastectomy radiotherapy (PMRT) for women with pT3N0M0 breast cancer is controversial. We sought to determine the benefit of PMRT in this cohort using the National Cancer Database (NCDB).MethodsWe analyzed women with pT3N0M0 breast cancer who received mastectomy with or without PMRT between 2004 and 2012. We excluded men, women ≤18 years, neoadjuvant or unknown radiation or chemotherapy status, unknown estrogen or progesterone receptor status, unknown surgical margin status, histology other than invasive ductal or lobular carcinoma, and if death occurred <3 months after diagnosis. A total of 4291 patients was included for analysis. Chi-squared analysis was used to compare patient characteristics. Univariate (UVA) and multivariate (MVA) Cox proportional hazards modeling was used to identify factors associated with survival. Propensity score matching was performed to address confounding variables. Survival analysis was performed using Kaplan-Meier and shared frailty models.ResultsOf the 4291 women analyzed, 2030 (47%) received PMRT. On MVA, PMRT (HR 0.72, p < 0.001), chemotherapy (HR 0.51, p < 0.001), and hormone therapy (HR 0.63, p < 0.001) were associated with improved overall survival (OS). After propensity score matching, a matched cohort of 2800 women was analyzed. At 5 years, OS was 83.7% and 79.8% with and without PMRT, respectively (p < 0.001). This difference in OS benefit increased with time. At 10 years, OS was 67.4% and 59.2% with and without PMRT, respectively.ConclusionsPMRT was associated with improved OS in women with pT3N0M0 breast cancer, which strongly suggests PMRT may provide a survival advantage and should be considered.     

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.     

Effect of pathologic stages on postmastectomy radiation therapy in breast cancer receiving neoadjuvant chemotherapy and total mastectomy: A Cancer Database Analysis

PurposeTo use pathologic indicators to determine which patients benefit from postmastectomy radiation therapy (PMRT) for breast cancer after neoadjuvant chemotherapy (NACT) and total mastectomy (TM).Patients and methodsWe enrolled 4236 patients with breast invasive ductal carcinoma who received NACT followed by TM. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals; independent predictors were controlled for or stratified in the analysis.ResultsAfter multivariate Cox regression analyses, the adjusted HRs derived for PMRT for all-cause mortality were 0.65 (0.52–0.81, P < 0.0001) and 0.58 (0.47–0.71, P < 0.0001) in postchemotherapy pathologic tumor stages T2–4 (ypT3–4) and postchemotherapy pathologic nodal stages N2–3 (ypN2–3), respectively. Moreover, adjusted HRs derived for PMRT with all-cause mortality were 0.51 (0.38–0.69, P < 0.0001), 0.60 (0.40–0.88, P = 0.0096), and 0.64 (0.48–0.86, P = 0.0024) in pathological stages IIIA, IIIB, and IIIC, respectively. Additionally, the PMRT group showed significant locoregional control irrespective of the pathologic response, even ypT0, ypN0, or pathological complete response (pCR), compared with the No-PMRT group. The multivariate analysis showed no statistical differences between the PMRT and No-PMRT groups for distant metastasis-free survival in any pathologic response of ypT0–4, ypN0–3, and pathologic American Joint Committee on Cancer stages pCR to IIIC.ConclusionFor patients with breast cancer ypT3–4, ypN2–3, or pathologic stages IIIA–IIIC receiving NACT and TM, benefit from PMRT if it is associated with OS benefits, regardless of the clinical stage of the disease. Compared with No-PMRT, PMRT improved locoregional recurrence-free survival, even pCR, in patients with breast cancer receiving NACT and TM.     

Locoregional recurrence after cystectomy in muscle invasive bladder cancer: Implications for adjuvant radiotherapy

PurposeWe report the patterns of locoregional recurrence (LRR) in muscle invasive bladder cancer (MIBC), and propose a risk stratification to predict LRR for optimizing the indication for adjuvant radiotherapy.Materials and MethodsThe study included patients of urothelial MIBC who underwent radical cystectomy with standard perioperative chemotherapy between 2013 and 2019. Recurrences were classified into local and/or cystectomy bed, regional, systemic, or mixed. For risk stratification modelling, T stage (T2, T3, T4), N stage (N0, N1/2, N3) and lymphovascular invasion (LVI positive or negative) were given differential weightage for each patient. The cohort was divided into low risk (LR), intermediate risk (IR) and high risk (HR) groups based on the cumulative score.ResultsOf the 317 patients screened, 188 were eligible for the study. Seventy patients (37.2%) received neoadjuvant chemotherapy (NACT) while 128 patients (68.1%) had T3/4 disease and 66 patients (35.1%) had N+ disease. Of the 55 patients (29%) who had a recurrence, 31 (16%) patients had a component of LRR (4% cystectomy bed, 11.5% regional 0.5% locoregional). The median time to LRR was 8.2 (IQR 3.3–18.8) months. The LR, IR and HR groups for LRR based on T, N and LVI had a cumulative incidence of 7.1%, 21.6%, and 35% LRR, respectively. The HR group was defined as T3, N3, LVI positive; T4 N1/2, LVI positive; and T4, N3, any LVI. The odds ratio for LRR was 3.37 (95% CI 1.16–9.73, P = 0.02) and 5.27 (95% CI 1.87–14.84, P = 0.002) for IR and HR respectively, with LR as reference.ConclusionLRR is a significant problem post radical cystectomy with a cumulative incidence of 35% in the HR group. The proposed risk stratification model in our study can guide in tailoring adjuvant radiotherapy in MIBC.     

Risk of Positive Sentinel Lymph Node After Neoadjuvant Systemic Therapy in Clinically Node-Negative Breast Cancer: Implications for Postmastectomy Radiation Therapy and Immediate Breast Reconstruction

Background

Residual axillary lymph node involvement after neoadjuvant systemic therapy (NST) is the determining factor for postmastectomy radiation therapy (PMRT). Preoperative identification of patients needing PMRT is essential to enable shared decision-making when choosing the optimal timing of breast reconstruction. We determined the risk of positive sentinel lymph node (SLN) after NST in clinically node-negative (cN0) breast cancer.

Methods

All cT1-3N0 patients treated with NST followed by mastectomy and SLNB between 2010 and 2016 were identified from the Netherlands Cancer Registry. Rate of positive SLN for different breast cancer subtypes was determined. Logistic regression analysis was performed to determine correlated clinicopathological variables with positive SLN.

Results

In total 788 patients were included, of whom 25.0% (197/788) had positive SLN. cT1-3N0 ER+HER2+, cT1-3N0 ER−HER2+ , and cT1-2N0 triple-negative patients had the lowest rate of positive SLN: 7.2–11.5%, 0–6.3%, and 2.9–6.2%, respectively. cT1-3N0 ER+HER2− and cT3N0 triple-negative patients had the highest rate of positive SLN: 23.8–41.7% and 30.4%, respectively. Multivariable regression analysis showed that cT2 (odds ratio [OR] 1.93; 95% confidence interval [CI] 1.01–3.96), cT3 (OR 2.56; 95% CI 1.30–5.38), grade 3 (OR 0.44; 95% CI 0.21–0.91), and ER+HER2− subtype (OR 3.94; 95% CI 1.77–8.74) were correlated with positive SLN.

Conclusions

In cT1-3N0 ER+HER2+, cT1-3N0 ER−HER2+, and cT1-2N0 triple-negative patients treated with NST, immediate reconstruction can be considered an acceptable option due to low risk of positive SLN. In cT1-3N0 ER+HER2− and cT3N0 triple-negative patients treated with NST, risks and benefits of immediate reconstruction should be discussed with patients due to the relatively high risk of positive SLN.

     

208例T1-2N1M0期乳腺癌改良根治术患者无病生存情况的危险因素分析

目的探究行改良根治术的T1-2N1M0期乳腺癌患者无病生存的影响因素。 方法回顾性分析2011年1月至2014年11月经改良根治术治疗208例T1-2N1M0期乳腺癌患者资料,统计术后截止2019年11月患者随访情况,并记录患者术后5年肿瘤转移、复发情况,以SPSS 22.00统计学软件进行数据处理。计数资料用[例(%)]表示,组间比较采用χ²检验;乳腺癌患者预后的相关因素行单因素和Cox多因素回归模型分析,P<0.05差异有统计学意义。 结果本次研究中208例患者均获得确切随访,无失访病例。其中复发、转移28例(13.5%),无转移复发180例(86.5%),患者5年无病生存率为86.5%;将单因素分析结果具有统计学意义的变量纳入Cox多因素回归模型。结果显示,年龄<45岁、组织学分级为III级、术后放疗、Ki-6 ≥30%为行改良根治术T1-2N1M0期乳腺癌患者复发转移的独立预后因素(P<0.05)。 结论年龄<45岁、组织学分级为III级、术后放疗、Ki-67≥30%是T1-2N1M0期乳腺癌患者行改良根治术后复发转移的独立危险因素,增加患者预后风险。     

Selection Criteria for Postmastectomy Radiotherapy in T1–T2 Tumors with 1 to 3 Positive Lymph Nodes

Background

Postmastectomy radiotherapy (PMRT) is well established in patients with ≥4 positive axillary lymph nodes (ALN); indications in 1 to 3 positive ALN remains controversial. We examined clinicopathologic criteria used for PMRT selection and compared locoregional recurrence (LRR), recurrence-free survival (RFS), and overall survival (OS) among patients with and without PMRT.

Methods

Between 1995 and 2006, a total of 1,331 patients with T1–T2 tumors and 1 to 3 positive ALN underwent mastectomy. We excluded T3/T4 tumors and neoadjuvant chemotherapy; we analyzed 1,087 patients (924 without PMRT, 163 with PMRT). Chi square testing compared clinicopathologic features between groups. The Kaplan–Meier method and Cox regression analysis examined the association between PMRT and LRR, RFS, and OS.

Results

PMRT patients were more likely to be ≤50 years old (p = 0.001) and to have larger tumors (p = 0.01), disease of a higher histologic grade (p = 0.03), lymphovascular invasion (LVI) (p < 0.0001), a greater number of positive ALN (p < 0.0001), extranodal invasion (p < 0.0001), and macroscopic ALN metastases (p < 0.0001). With a median follow-up of 7 years, PMRT and no-PMRT groups were similar in LRR (p = 0.57), RFS (p = 0.70), and OS (p = 0.28). On multivariate analysis of the no-PMRT group, age ≤50 years (p = 0.002) and presence of LVI (p < 0.0001) were associated with LRR. Stratified by age and LVI, patients ≤50 years old and with LVI had the highest 5-year LRR, 10.1 versus 1.1 %, than in patients >50 years old without LVI (p < 0.001).

Conclusions

By using clinicopathologic features, clinicians delivered PMRT to a select group of patients with T1–T2 tumors and 1 to 3 positive ALN, resulting in similarly low rates of 5-year LRR. Among patients not receiving PMRT, age ≤50 years and LVI were associated with increased LRR rates and warrant PMRT consideration.     

Conditional Survival After Surgical Treatment of Melanoma: An Analysis of the Surveillance, Epidemiology, and End Results Database

Background

Survival curves following surgical treatment of cutaneous melanoma are heavily influenced by early deaths. Therefore, survival estimates may be misleading for long-term cancer survivors. We examined whether conditional survival (CS) is more accurate in predicting long-term melanoma survival.

Methods

We used the Surveillance, Epidemiology, and End Results database (1992–2005) to identify patients who underwent surgical treatment for melanoma. We included patients with T2–T4 disease and with known nodal status. Patients were stratified into low-risk (T2-3N0M0) and high-risk (T4N0M0 or T2-4N1-3M0) categories. We defined CS as time-specific estimates conditioned on living to a certain point in follow-up, and calculated 10-year cancer-specific survival curves conditioned on annual survival. We adjusted for potential confounders using a Cox proportional hazards regression model (α = 0.05).

Results

A total of 8647 patients met inclusion criteria (low-risk, 5987 [69.2%]; high-risk, 2660 [30.8%]). At diagnosis, low-risk patients had a significantly better 10-year survival rate (low-risk, 79.6%; high-risk, 41.2%; P < 0.001). On CS analysis, survival differences remained until 8 years after treatment, after which 10-year cancer-specific survival rates were no longer significantly different (P = 0.51) for low-risk (95.4%) and high-risk (91.7%) groups. Multivariate analysis demonstrated that age, gender, location, and ulceration (initial predictors of survival) were no longer predictive after 8 years of survival.

Conclusions

For patients who survive 8 years after surgical treatment of melanoma, CS data become discordant with traditionally used estimates. Our findings have important implications for patient counseling, as high-risk melanoma survivors may require no more intensive surveillance than low-risk survivors 8 years after treatment.