5-year Locoregional Recurrence Rate Research Articles

The impact of loco-regional treatment modality on the outcomes in breast cancer patients younger than forty years of age

PurposeTo determine the impact of the loco-regional treatment modality, on the loco-regional recurrence (LRR) rates and overall survival (OS) in breast cancer patients younger than 40 years.MethodsData of 623 breast cancer patients younger than 40 years of age were retrospectively reviewed. Patients were stratified according to the locoregional treatment approach into three groups: the mastectomy group (M), the mastectomy followed by radiation therapy group (MRX) and the breast conservative therapy group (BCT).ResultsMedian follow-up was 72 months (range, 6-180). Two hundred and nine patients were treated with BCT, 86 with MRM and 328 with MRX. The 10-year rate LRR rates according to treatment modality were: 13.4% for BCT, 15.1% for MRM and 8.5% for MRX (p 0.106). On univariate analysis, T stage (p 0.009), AJCC stage (p 0.047) and Her 2 status (p 0.001) were associated with LRR. Ten-year overall survival (OS) was 72.7% (78.5% in the BCT group, 69.8% in the MRM group and 69.8% in the MRX group, p 0.072).On Univariate analysis, age < 35 (p 0.032), grade III (p 0.001), N3 stage (p 0.001), AJCC stage III (p 0.005), ER negative status (0.04), Her 2-status positive (0.006) and lack of chemotherapy administration (p 0.02) were all predictors of increased mortality.ConclusionFor patients younger than 40 years of age, similar LRR and overall survival outcomes were achieved using BCT, M or MRX. Young age at diagnosis should not be used alone in recommending one loco-regional treatment approach over the others.

Clinicopathological characteristics and prognostic factors in invasive micropapillary carcinoma of the breast.

Invasive micropapillary carcinoma (IMPC) treatment only relies on the standard treatment of nonspecific invasive breast cancer (NSIBC), and it remains controversial whether the survival of patients improves. Therefore, this study aimed to analyze the clinicopathological features of IMPC and to investigate the factors affecting its prognosis. This retrospective cohort study included 104 IMPC patients who met the study's inclusion criteria out of a total of 4,532 patients with invasive breast cancer between January 2015 and December 2019. A contemporaneous cohort of 230 patients with non-specific invasive breast cancer (NSIBC) who underwent surgery was identified and matched using propensity scores. The survival rate for patients with IMPC ranged from 1.12% to 7.03%. Statistically significant differences were observed in the proportion of endocrine treatment, lymphatic invasion, estrogen receptor (ER)-positive rate, molecular subtypes, molecular typing, and 5-year loco-regional recurrence-free survival (LRRFS) between the two cohorts (p < 0.05). The univariate analysis showed that T stage, N stage, lymphatic invasion, vascular invasion, ER-positive rate, and progesterone receptor (PR)-negative rate were all prognosis risk factors (p < 0.05) for IMPC. Furthermore, the multivariate analysis indicated that lymphatic invasion and N stage were independent prognostic factors (p < 0.05). The incidence of micropapillary IMPC, among other pathological subtypes, is steadily increasing. ER-positive and PR-positive rates, as well as luminal subtypes, are frequent, with a concurrent increase in the 5-year locoregional recurrence rate. It would be interesting to compare the effect following these therapeutic modifications in larger cohorts in future studies.

Oncotype Recurrence Score (RS) at the Extremes of Tumor Size: Which Drives Clinical Outcomes?

Tumor size is an established and independent risk factor for local-regional recurrence (LRR) and distant recurrence (DM). More recently, the recurrence score calculated from a 21-gene expression assay (Oncotype DXTM, Exact Sciences) has also been correlated with LRR and DM. We sought to determine the impact of the interaction between tumor size and Oncotype RS, particularly when the variables are in discrepancy with each other. More specifically, we evaluated clinical outcomes in patients with small tumors (≤1 cm) and high RS (≥26) and, separately, in patients with large tumors (>5 cm) with low RS. Between 2008 and 2020, 310 patients were identified retrospectively as having been treated for early-stage, hormone-receptor positive, Her2-negative breast cancers with tumor size ≤1 cm that were node-negative and had RS ≥ 26 at our institution. In addition, 64 patients were identified with tumor size >5 cm and RS < 26 (irrespective of nodal status). Locoregional recurrence rates (LRR) and invasive recurrence rates (composite of LRR and distant recurrence) were estimated using the Kaplan-Meier method. Patient characteristics are shown in Table 1. In the group of patients with small tumors and high RS, the 5- and 10-year invasive recurrence rates with 95% CI were 8% (4.2-12) and 17% (8.2-26). The 5- and 10-year locoregional recurrence rates with 95% CI were 5.8% (2.7-8.8) and 15% (6.2-23). In the group of patients with large tumors and low RS, 10-year rates could not be estimated with the available data. The 5- and 8-year invasive recurrence rates with 95% CI were 3.2% (0-7.5) and 3.2% (0-7.5). The 5- and 8-year locoregional recurrence rates with 95% CI were 1.6% (0-4.7) and 1.6% (0-4.7). Our findings suggest that patients with small tumors and high RS are at a higher risk for LRR compared to the average ≤1 cm node-negative breast cancer based on published data on the effect of tumor size on LRR and DM. Similarly, tumors larger than 5 cm with low RS appear to behave indolently and in a manner consistent with more favorable risk (despite their large size). These findings may have important implications for the tailoring of local-regional treatment strategies.

Breast-conserving surgery versus mastectomy for treatment of breast cancer after neoadjuvant chemotherapy.

To compare recurrence and survival outcomes between breast-conserving surgery (BCS) and mastectomy after neoadjuvant chemotherapy (NACT). The data of 730 patients who underwent NACT between 2000 and 2014 were retrospectively reviewed. A total of 104 (14.2%) patients received BCS and 626 (85.8%) received mastectomy. Locoregional recurrence (LRR), distant metastases (DM), disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS) were analyzed using the Kaplan-Meier method. The impact of BCS versus mastectomy on outcomes was assessed by multivariate Cox models. Inverse probability of treatment weighting (IPTW) was used to balance covariates between the two groups. The median follow-up of BCS and mastectomy groups were 86.5 and 87.4 months, respectively. There were significant differences in distribution of most baseline characteristics between two groups. Compared with those who underwent mastectomy, the patients with BCS had similar 5-year LRR, DM, and DFS rates, but had significantly higher 5-year BCSS (98.9% vs. 90.4%, P = 0.005) and OS (98.9% vs. 90.1%, P = 0.003) rates. Multivariate analysis also showed that BCS significantly improved BCSS (HR = 0.27, 95% CI: 0.08-0.85, P = 0.025) and OS (HR = 0.25, 95% CI: 0.08-0.79, P = 0.018). After IPTW adjustment, the LRR, DM, DFS, BCSS and OS between two groups had no significant differences. The recurrence and survival outcomes are comparable with BCS and mastectomy. Thus, BCS is a safe treatment option for selected breast cancer patients after NACT.

Prognostic Value of Lymphovascular Invasion in Patients With Pyriform Sinus Carcinoma Treated With Surgery Plus Adjuvant Chemo-/Radiotherapy.

We aimed to determine the prognostic value of lymphovascular invasion (LVI) in pyriform sinus carcinoma (PSC) after primary surgery with adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). Patients who underwent primary surgery at our institution between 2000 and 2018 were included in this study and retrospectively analyzed. The endpoints were locoregional recurrence (LRR), distant metastasis (DM), and disease-specific survival (DSS). We reviewed 117 patients with PSC. LVI was identified in 29 patients (24.8%). The 5-year LRR rate, DM rate, and DSS rate were 29.4%, 31.7%, and 45.9%, respectively. Tumors with LVI were associated with a significantly higher LRR (P = 0.002, HR 3.678, 95% CI 1.646-8.218) and DM (P = 0.003, HR 3.666, 95% CI 1.543-8.709) and a lower DSS (P = 0.001, HR 2.814, 95% CI 1.519-5.213) in multivariate analysis. LVI is a significant predictor of poor prognosis in patients with PSC treated with surgery plus adjuvant RT/CCRT.

Abstract P4-02-12: Validation of Profile for the Omission of Local Adjuvant Radiotherapy (POLAR) in early-stage invasive breast cancer patients of the Scottish Conservation Trial

Abstract Background: Adjuvant whole breast radiotherapy (RT) is provided to almost all women with early-stage invasive breast cancer after breast conserving surgery and appropriate systemic therapy. While there is increasing interest to personalize the use of RT based on molecular profiling, to date, there is no molecular signature available to reliably assess the benefit of radiotherapy after surgical resection. Here we assess the ability of a 16-gene signature named Profile for the Omission of Local Adjuvant Radiotherapy (POLAR) to identify who may be suitable candidates for radiotherapy omission in patients of the Scottish Conservation Trial. Methods: The POLAR signature was applied to archival tissue from the Scottish Conservation Trial, which randomized 585 patients with stage I-II breast cancer, tumor size &amp;lt; 4 cm, and age ≤70 years old to receive RT or not. The archival tissue was measured for ER (ER+ &amp;gt;10%), PgR (PgR+ ≥20%), Ki67 (Ki67 high ≥14%), and HER2 (HER2+ defined as HER2 over-expressed or amplified). 26% received adjuvant chemotherapy, the remainder received tamoxifen 20 mg/daily for 5 years. Cox models for the locoregional recurrence (LRR) endpoint tested the association between treatment arms separately for patients with a low and high POLAR score using a pre-specified cut point. Cumulative incidences were computed, with distant metastasis and death without recurrence considered competing events. Results: 224 patients had tissue available and complete clinical data for analysis, 40 (18%) were node-positive. The distribution of clinicopathologic variables between the RT and no RT arms remained balanced. 43% were ER+/PgR+/Ki67 low/HER2-, 31% were ER+/HER2-/Ki67 high or PgR-, 5% were HER2+, and 13% were triple negative. The continuous standardized POLAR score was prognostic for LRR in the no RT arm after adjusting for relevant covariates (HR=1.78 [1.20-2.64], p=0.003). For patients with a POLAR-high score, the 10-year LRR rate was 31% [21%-42%] for patients not receiving RT and 8% [3%-15%] for patients receiving RT (HR 0.36 [0.19-0.69], p=0.0022). For patients with a POLAR low score, the 10-year LRR rates were 20% [10%-33%] for patients not receiving RT and 6% [1%-18%] for patients receiving RT; HR=0.28 [0.08-0.98], p=0.046). In the subgroup of node-negative patients with ER+/HER2-negative tumors (N=137), there was a statistically significant RT benefit for patients with a POLAR high score (HR=0.31 [0.11-0.88], p=0.028) but not for patients with a POLAR low score (HR=0.5 [0.1-2.4], p=0.39). Conclusions: For patients with early-stage invasive breast cancer treated with breast-conserving surgery without RT, POLAR is prognostic for LRR and may refine the selection of “low risk” for omission of RT. Citation Format: Karen J. Taylor, John MS Bartlett, John Bennett, S. Laura Chang, Bradley Arrick, Frederick Baehner, Joseph F. Loane, Tammy Piper, Elizabeth Mallon, Joanna Dunlop, Wilma J. Jack, Jacqueline Caldwell, Ian Kunkler, Linda J. Williams, Corey W. Speers, Felix Y. Feng, Lori Pierce, David A. Cameron. Validation of Profile for the Omission of Local Adjuvant Radiotherapy (POLAR) in early-stage invasive breast cancer patients of the Scottish Conservation Trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-02-12.

Abstract OT1-12-02: Preliminary report of the PRECISION Trial (Profiling Early Breast Cancer for Radiotherapy Omission): A Phase II Study of Breast-Conserving Surgery Without Adjuvant Radiotherapy for Favorable-Risk Breast Cancer

Abstract Background: Breast conserving surgery (BCS) is typically followed by adjuvant radiotherapy (RT) based on several landmark trials demonstrating improvements in disease control and survival. Since completion of these historical trials, the advent of molecular subtyping has revealed that breast cancer is not a single disease entity, but rather a class of cancers with differential risk profiles. We evaluated whether RT could be safely omitted following BCS for patients with the most favorable subtype as defined by the Prosigna PAM50 assay. Methods: We conducted a multicenter prospective single-arm cohort study with IRB approval and an FDA investigational device exemption (IDE). Eligible patients were women 50 to 75 years of age (inclusive) who had undergone BCS revealing tumors ≤2cm in size, that were estrogen or progesterone receptor positive (HR+), HER2 negative, grade 1-2, node negative (N0), with negative excision margins (no ink on tumor). Intent to take endocrine therapy was required. Upon registration, tumors were submitted for central Prosigna testing and those with Risk of Recurrence (ROR) score ≤40 were deemed eligible for the investigational omission of RT. The primary endpoint was the 5-year locoregional recurrence rate (LRR). Anticipating a total of 345 RT-omitting patients to enroll over 3.5 years, the study was designed with 90% power to exclude a 5-year LRR of 5% using a one-sample exponential test with one-sided type I error of 0.025. Results: From 2016 to 2020, 671 patients were registered from 13 centers, inclusive of affiliated regional network sites. Of these, 382 patients had a ROR Score ≤40 and opted to forego RT, comprising the main intention-to-treat (ITT) study population. Median age was 65 years (range 50 to 75), and median tumor size was 0.9 cm (range 0.1 to 2.0 cm). At a median follow-up of 26.9 months, 12 events were observed: 4 patients had ipsilateral in-breast recurrences, 7 had contralateral breast cancers, and 1 developed an unrelated melanoma. There were no regional-nodal or distant recurrences. The 2-year cumulative rate of LRR was 0.3% (95% CI: 0 – 1.0%). Of the 4 ipsilateral breast recurrences, 2 were in the same quadrant as the original primary tumor. Conclusion: In this preliminary report of the PRECISION trial, patients 50-75 years of age undergoing BCS and endocrine therapy for pT1N0 HR+ HER2-negative breast cancer with ROR score ≤40 had exceedingly low rates of LRR in the absence of adjuvant RT at a median follow-up of 26.9 months. Additional follow-up is required to determine whether these favorable results are durable. Citation Format: Lior Z. Braunstein, Julia Wong, Deborah A. Dillon, Yu-Hui Chen, Paul Catalano, Oren Cahlon, Mahmoud B. El-Tamer, Rachel Jimenez, Atif Khan, Carmen Perez, Rinaa Punglia, Ron Shiloh, Laura Warren, David Wazer, Jean Wright, Elizabeth Buckley, Tari King, Simon Powell, Eric Winer, Jennifer Bellon. Preliminary report of the PRECISION Trial (Profiling Early Breast Cancer for Radiotherapy Omission): A Phase II Study of Breast-Conserving Surgery Without Adjuvant Radiotherapy for Favorable-Risk Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-12-02.

Risk factors to identify the indication for regional nodal irradiation in T1-2N1M0 breast cancer: A joint analysis of 4,243 real-world cases from two institutions.

The aim of this study is to evaluate the role of regional nodal irradiation (RNI) in patients with T1-2N1M0 breast cancer and to identify the subgroup that could benefit from RNI. A total of 4,243 women with pT1-2N1M0 breast cancer treated at two institutions in China were retrospectively reviewed. Survival rates were calculated by the Kaplan-Meier method and compared by the log-rank test. The association of risk factors with survival outcomes was evaluated using multivariable proportional hazards regression. A total of 932 patients (22.0%) received RNI. At a median follow-up of 5.9 years, the 5-year locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) rates were 4.0% and 7.2% (P = 0.001), 13.2% and 10.6% (P = 0.465), 85.0% and 84.7% (P = 0.131), and 93.9% and 92.8% (P = 0.004) in the RNI and non-RNI groups, respectively. Multivariate analysis revealed that RNI was an independent prognostic factor for lower LRR (P = 0.001) and longer DFS (P = 0.013). Patients were stratified into low-, intermediate-, and high-risk groups based on the eight non-therapeutic risk factors. RNI significantly decreased the 5-year LRR (2.2% vs. 7.0%, P = 0.001) and improved the 5-year DFS (88.8% vs. 84.9%, P = 0.015) and OS (95.8% vs. 93.9%, P = 0.010) in the intermediate-risk group. However, neither the low-risk group nor the high-risk group had survival benefit from RNI. T1-2N1M0 breast cancer is a heterogeneous disease. We found that RNI only improved survival in the intermediate-risk group. It might be omitted in low-risk patients, and the role of RNI in high-risk patients needs further study.

Effects of gross tumor volume and radiation dose on survival and locoregional recurrence in early-stage extranodal NK/T-cell lymphoma treated with intensity-modulated radiation therapy.

To investigate the prognostic value of gross tumor volume (GTV) in early-stage extranodal NK/T-cell lymphoma (ENKTCL) treated with intensity-modulated radiation therapy (IMRT) and explore the interactive effect of GTV and radiotherapy (RT) dose on locoregional recurrence (LRR). The data of 319 early-stage ENKTCL patients who underwent IMRT were reviewed retrospectively. Overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) were estimated using Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards regression was performed to identify independent risk factors for survival outcomes. Penalized spline regression was used to flexibly model the association of continuous predictors (GTV and RT dose) with mortality, progression, and relapse. The 5-year OS, PFS, and LRC for the entire cohort were 72.9, 64.4, and 89.9%, respectively. The risks of disease mortality, progression, and recurrence increased steadily with increasing GTV. Patients with GTV < 35mL had significantly higher 5-year OS (83.0% vs. 59.4%; P < 0.001), PFS (76.7% vs. 48.4%; P < 0.001), and lower 5-year cumulative LRR rate (4.9% vs. 14.5%; P = 0.004), than patients with GTV ≥ 35mL. The risk of LRR was low with RT doses of 50-56Gy, independent of GTV. For patients with GTV ≥ 35mL, dose ≥ 56Gy was not associated with decreased LRR. Larger GTV is associated with worse survival and higher LRR in early-stage ENKTCL patients treated with IMRT. A dose of 50-56Gy may be appropriate to achieve lower risk of LRR, regardless of GTV.

Cervical cancer survival times in Africa.

Accessibility to quality healthcare, histopathology of tumor, tumor stage and geographical location influence survival rates. Comprehending the bases of these differences in cervical cancer survival rate, as well as the variables linked to poor prognosis, is critical to improving survival. We aimed to perform the first thorough meta-analysis and systematic review of cervical cancer survival times in Africa based on race, histopathology, geographical location and age. Major electronic databases were searched for articles published about cervical cancer survival rate in Africa. The eligible studies involved studies which reported 1-year, 3-year or 5-year overall survival (OS), disease-free survival (DFS) and/or locoregional recurrence (LRR) rate of cervical cancer patients living in Africa. Two reviewers independently chose the studies and evaluated the quality of the selected publications, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA-P). We used random effects analysis to pooled the survival rate across studies and heterogeneity was explored via sub-group and meta-regression analyses. A leave-one-out sensitivity analysis was undertaken, as well as the reporting bias assessment. Our findings were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA-P). A total of 16,122 women with cervical cancer were covered in the 45 articles (59 studies), with research sample sizes ranging from 22 to 1,059 (median = 187.5). The five-year overall survival (OS) rate was 40.9% (95% CI: 35.5-46.5%). The five-year OS rate ranged from 3.9% (95% CI: 1.9-8.0%) in Malawi to as high as 76.1% (95% CI: 66.3-83.7%) in Ghana. The five-year disease-free survival rate was 66.2% (95% CI: 44.2-82.8%) while the five-year locoregional rate survival was 57.0% (95% CI: 41.4-88.7%). To enhance cervical cancer survival, geographical and racial group health promotion measures, as well as prospective genetic investigations, are critically required.

Comparison of Breast-Conserving Surgery vs. Mastectomy for Patients with Breast Cancer after Neoadjuvant Chemotherapy

<h3>Purpose/Objective(s)</h3> To compare recurrence and survival outcomes between breast-conserving surgery (BCS) and mastectomy after neoadjuvant chemotherapy (NACT). <h3>Materials/Methods</h3> A total of 730 eligible patients who underwent NACT between 2000 and 2014 were retrospectively reviewed. Of those, 104 (14.2%) patients received BCS and 626 (85.8%) patients received mastectomy. Locoregional recurrence (LRR), distant metastases (DM), disease-free survival (DFS), Breast cancer - specific survival (BCSS) and overall survival (OS) were estimated using the Kaplan-Meier method. The impact of BCS versus (vs) mastectomy on outcomes was assessed by multivariate Cox models and inverse probability of treatment weighting (IPTW) method by adjusting for age, clinical T stage, clinical N stage, NACT cycles, histological grade, lymphovascular invasion (LVI), molecular subtype/trastuzumab, ypT (pathologic tumor stage after NACT), ypN (pathologic lymph node stage after NACT), endocrine therapy, and adjuvant chemotherapy. Recurrence and survival curves before or after weighting were compared with the log rank test. <h3>Results</h3> The median follow-up was 87.4 months. The 5-year LRR, DM, DFS, BCSS and OS rates after BCS and mastectomy were 6.9% vs 7.6% (P = 0.805), 10.8% vs 19.9% (P = 0.145), 83.4% vs 78.2% (P = 0.514), 98.9% vs 90.4% (P = 0.005) and 98.9% vs 90.1% (P = 0.003), respectively. There were significant differences in distribution of most baseline characteristics between the BCS and mastectomy group. After IPTW adjustment, the clinical characteristics between two groups were comparable. Multivariate analysis showed that BCS had no significant impact on LRR (HR 1.08, 95% CI 0.48-2.43, P = 0.849), DM (HR 0.82, 95% CI 0.49-1.40, P = 0.473) and DFS (HR 1.12, 95% CI 0.70-1.80, P = 0.626) compared with mastectomy, but BCS significantly improved BCSS (HR 0.29, 95% CI 0.09-0.92, P = 0.035) and OS (HR 0.27, 95% CI 0.08-0.86, P = 0.027) compared with mastectomy. After IPTW adjustment, the results of 5-year LRR, DM, DFS remained the same, which were 10.0% vs 7.3% (P = 0.598), 11.7% vs 19.0% (P = 0.341), 78.6% vs 79.1% (P = 0.908) for BCS and mastectomy groups, respectively. The 5-year BCSS and OS were better in the BCS group than in the mastectomy group, but the difference was no longer statistically significant (BCSS: 99.7% vs. 90.8%, <i>P</i> = 0.095 and OS: 99.7% vs. 90.6%, <i>P</i> = 0.083). <h3>Conclusion</h3> Locoregional and distant control and DFS are comparable with BCS and mastectomy, but BCSS and OS may be better with BCS. Thus, BCS is a safe treatment option for selected breast cancer patients after NACT.

De-escalation of radiotherapy after primary chemotherapy in cT1-2N1 breast cancer (RAPCHEM; BOOG 2010-03): 5-year follow-up results of a Dutch, prospective, registry study.

Primary chemotherapy in breast cancer poses a dilemma with regard to adjuvant locoregional radiotherapy, as guidelines for locoregional radiotherapy were originally based on pathology results of primary surgery. We aimed to evaluate the oncological safety of de-escalated locoregional radiotherapy in patients with cT1-2N1 breast cancer treated with primary chemotherapy, according to a predefined, consensus-based study guideline. In this prospective registry study (RAPCHEM, BOOG 2010-03), patients referred to one of 17 participating radiation oncology centres in the Netherlands between Jan 1, 2011, and Jan 1, 2015, with cT1-2N1 breast cancer (one to three suspicious nodes on imaging before primary chemotherapy, of which at least one had been pathologically confirmed), and who were treated with primary chemotherapy and surgery of the breast and axilla were included in the study. The study guideline comprised three risk groups for locoregional recurrence, with corresponding locoregional radiotherapy recommendations: no chest wall radiotherapy and no regional radiotherapy in the low-risk group, only local radiotherapy in the intermediate-risk group, and locoregional radiotherapy in the high-risk group. Radiotherapy consisted of a biologically equivalent dose of 25 fractions of 2 Gy, with or without a boost. During the study period, the generally applied radiotherapy technique in the Netherlands was forward-planned or inverse-planned intensity modulated radiotherapy. 5-year follow-up was assessed, taking into account adherence to the study guideline, with locoregional recurrence rate as primary endpoint. We hypothesised that 5-year locoregional recurrence rate would be less than 4% (upper-limit 95% CI 7·8%). This study was registered at ClinicalTrials.gov, NCT01279304, and is completed. 838 patients were eligible for 5-year follow-up analyses: 291 in the low-risk group, 370 in the intermediate-risk group, and 177 in the high-risk group. The 5-year locoregional recurrence rate in all patients was 2·2% (95% CI 1·4-3·4). The 5-year locoregional recurrence rate was 2·1% (0·9-4·3) in the low-risk group, 2·2% (1·0-4·1) in the intermediate-risk group, and 2·3% (0·8-5·5) in the high-risk group. If the study guideline was followed, the locoregional recurrence rate was 2·3% (0·8-5·3) for the low-risk group, 1·0% (0·2-3·4) for the intermediate-risk group, and 1·4% (0·3-4·5) for the high-risk group. In this study, the 5-year locoregional recurrence rate was less than 4%, which supports our hypothesis that it is oncologically safe to de-escalate locoregional radiotherapy based on locoregional recurrence risk, in selected patients with cT1-2N1 breast cancer treated with primary chemotherapy, according to this predefined, consensus-based study guideline. Dutch Cancer Society. For the Dutch translation of the abstract see Supplementary Materials section.

Axillary nodal metastasis and resection margins as predictors of Loco Regional Recurrence in Breast Cancer Patients.

Surgical resection margins (RM), axillary nodal involvement and lymph node ratio (LNR) determine loco-regional control (LRC) in breast cancer management. Late presentation precludes breast conservation therefore surgical option is usually mastectomy and adjuvant chemoradiation minimize loco-regional recurrence (LRR). We investigated the prognostic role of lymph nodes positive for malignancy (pN), LNR and RM on LRR of breast cancer in a tertiary hospital in Ibadan, Nigeria. Longitudinal cohort study of 225 females with breast carcinoma managed and followed up for 5-years with end point of LRR or not. Chi-square test and logistic regression analysis were used to evaluate the interaction of resection margin and proportion of metastatic lymph nodes with LRR. The receiver-operator curve was plotted to determine the proportion of metastatic lymph nodes which predicted LRR. Ninety-nine percent had modified radical mastectomy and 163 (72.4%) had negative resection margins. A mean of 11 axillary lymph nodes were harvested at surgery. The age, positive resection margin and number of harvested nodes with malignant cells are associated with LRR. The overall 5-year LRR rate was 16%. LRR is dependent on lymph node involvement as well as and tumor aggressiveness.

Long-term survival rates of patients with nasopharyngeal carcinoma treated by radiochemotherapy: a retrospective cohort study

BackgroundNasopharyngeal cancer (NPC) is showing an increasing incidence in Iran. Radiation is the main treatment of this cancer. Use of new techniques such as intensity-modulated radiotherapy (IMRT) is on the rise. Here, we aimed to evaluate the oncological outcomes of NPC patients treated with three-dimensional conformal radiotherapy (3DCRT) for a more reliable comparison with IMRT in the future.ResultsWe reviewed the medical records of 106 patients with NPC treated by definitive radiotherapy from 2007 to 2016. Patients were treated with 70 Gy in 2-Gy fractions. Twenty-one patients died during the follow-up period. Twenty-nine patients suffered from locoregional or distant recurrences. Of these, 6 recurred after 2 years of treatment completion. The 2-year and 5-year overall survival rates were 81% and 76%, respectively. The 2-year and 5-year progression-free survival rates were 72% and 63%, respectively. The 5-year locoregional recurrence and distant metastasis-free survival rates were 68% and 69%, respectively.ConclusionDue to high survival rates of NPC and the importance of receiving planned total dose of RT, the treatment-related toxicity and quality of life are critical considerations both for patients during active treatment and for survivors.

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

ObjectiveTo clarify the effect of postmastectomy radiotherapy (PMRT) on pT1-2N1 breast cancer patients with different molecular subtypes. MethodsWe retrospectively analyzed the data of 5442 patients with pT1-2N1 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 pT1-2N1 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.

Risk Factors to Identify the Indication for Regional Nodal Irradiation in T1-2N1M0 Breast Cancer: A Joint Analysis of 4243 Real-World Cases From Two Institutions

To evaluate the role of regional nodal irradiation (RNI) in patients with T1-2N1M0 breast cancer and identify the subgroup that could benefit from RNI.A total of 4243 women with T1-2N1M0 breast cancer treated at two institutions were retrospectively reviewed. Among them, 3858 (90.9%) received mastectomy and 385 (9.1%) received breast-conserving surgery. A total of 932 (22.0%) patients received RNI. Locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) rates were calculated by the Kaplan-Meier method and compared by log-rank test. The association of risk factors with survival outcomes was evaluated using multivariable proportional hazards regression.At a median follow-up of 5.9 years (interquartile range: 4.1-8.4), the 5-year LRR, DM, DFS, and OS rates were 4.0% and 7.2% (P = 0.001), 13.2% and 10.6% (P = .465), 85.0% and 84.7% (P = .131), and 93.9% and 92.8% (P = 0.004) in the RNI and non-RNI groups, respectively. Multivariate analysis revealed that RNI was an independent prognostic factor for lower LRR (P = 0.001) and longer DFS (P = 0.013). Patients were stratified into low-, intermediate-, and high-risk groups based on eight non-therapeutic risk factors. RNI significantly decreased the 5-year LRR (2.2% vs. 7.0%, P = 0.001) and improved the 5-year DFS (88.8% vs. 84.9%, P = 0.015) and OS (95.8% vs. 93.9%, P = 0.010) in the intermediate-risk group. On the other hand, RNI only decreased LRR in high-risk group, and had no impact on low-risk group.T1-2N1M0 breast cancer is a heterogeneous disease. We found that RNI only improved survival in the intermediate-risk group. It might be omitted in low-risk patients, and the role of RNI in high-risk patients needs further study.

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.

Risk Factors and Patterns of Locoregional Recurrence after Radical Nephrectomy for Locally Advanced Renal Cell Carcinoma.

PurposeWe aimed to investigate the risk factors and patterns of locoregional recurrence (LRR) after radical nephrectomy (RN) in patients with locally advanced renal cell carcinoma (RCC).Materials and MethodsWe retrospectively analyzed 245 patients who underwent RN for non-metastatic pT3–4 RCC from January 2006 to January 2016. We analyzed the risk factors associated with poor locoregional control using Cox regression. Anatomical mapping was performed on reference computed tomography scans showing intact kidneys.ResultsThe median follow-up duration was 56 months (range, 1 to 128 months). Tumor extension to renal vessels or the inferior vena cava (IVC) and Fuhrman’s nuclear grade IV were identified as independent risk factors of LRR. The 5-year actuarial LRR rates in groups with no risk factor, one risk factor, and two risk factors were 2.3%, 19.8%, and 30.8%, respectively (p < 0.001). The locations of LRR were distributed as follows: aortocaval area (n=2), paraaortic area (n=4), retrocaval area (n=5), and tumor bed (n=11). No LRR was observed above the celiac axis (CA) or under the inferior mesenteric artery (IMA).ConclusionTumor extension to renal vessels or the IVC and Fuhrman’s nuclear grade IV were the independent risk factors associated with LRR after RN for pT3–4 RCC. The locations of LRR after RN for RCC were distributed in the tumor bed and regional lymphatic area from the bifurcation of the CA to that of the IMA.

History of dysplasia and primary site associated with recurrence in T1N0 oral squamous cell carcinoma

Recurrent disease occurs in a significant proportion of early-stage oral squamous cell carcinoma (OSCC) despite removal of the entire tumor with clear surgical margins. Our study sought to identify clinicopathologic factors that increase the risk of locoregional recurrence in T1N0 OSCC. We conducted an observational retrospective analysis of 65 cases of T1N0 OSCC over a period of 13 years. For each case, we examined the clinical presentation, histopathologic appearance, and treatment characteristics of interest to evaluate the association between these variables and locoregional recurrence. The 5-year and 10-year locoregional recurrence rates were 29.2% and 33.8%, respectively. Individuals with prior oral dysplasia had significantly higher odds for locoregional recurrence (P < .01) and reduced 5-year disease-free survival rates (P < .01). OSCC of the tongue and floor of the mouth had lower recurrence odds than carcinomas of the gingiva, buccal mucosa, and palate (P < .05). Histologic grade (P=.80), depth of invasion (P=.82), and elective neck dissection (P=.80) did not appear to influence locoregional recurrence for T1N0 tumors. Given the morbidity and mortality associated with OSCC, understanding of the clinicopathologic factors associated with recurrent disease may lead to improved treatment and follow-up protocols for a subset of early-stage patients.

The Effect of Postmastectomy Radiotherapy on Breast Cancer Patients After Neoadjuvant Chemotherapy by Molecular Subtype.

The effect of postmastectomy radiotherapy (PMRT) on patient outcomes after neoadjuvant chemotherapy (NAC) remains controversial. We aimed to establish a model to identify the subsets benefiting from PMRT and to examine the effect of PMRT according to molecular subtype. We retrospectively analyzed 1118 cT1-4cN0-3M0 breast cancer patients treated with NAC and mastectomy. A nomogram predicting locoregional recurrence (LRR) was established based on 418 unirradiated patients, and X-tile analysis was performed to divide the patients into two risk groups. The effect of PMRT on LRR, distant recurrence (DR), and breast cancer mortality (BCM) was estimated for patients with different molecular subtypes in two risk groups. A nomogram predicting LRR was developed using six factors: histologic classification, lymphovascular invasion, ypT stage, ypN stage, estrogen receptor status, and Ki-67 expression. Our study found that PMRT correlated with lower 5-year LRR, DR, and BCM rates for the high-risk group; however, no significant improvement in these endpoints was observed in the low-risk group. Among patients with high risk, subgroup analysis showed that LRR control was improved after PMRT for the human epidermal growth factor receptor 2 (HER2)-negative/hormone receptor (HR)-positive (HER2-/HR+), HER2-positive (HER2+)/HR+, and HER2-/HR-negative (HR-) subtypes, with hazard ratios of 0.113 (95% confidence [CI] 0.034-0.379; p<0.001), 0.159 (95% CI 0.038-0.671; p=0.017), and 0.243 (95% CI 0.088-0.676; p=0.007), respectively, but not for the HER2+/HR- subtype (p=0.468). We built a nomogram showing favorable risk quantification and patient stratification. Patients in the high-risk group benefited from PMRT, but patients in the low-risk group did not. PMRT may show different benefits for each molecular subtype.