Cumulative Incidence Of Locoregional Recurrence Research Articles

Predicting locoregional recurrence in triple-negative breast cancer using novel molecular subtyping.

e12549 Background: Triple-negative breast cancer (TNBC) presents a poorer prognosis compared to other breast cancer subtypes, characterized by a higher likelihood of early recurrence and increased incidence of visceral metastases. Evidence from numerous randomized clinical trials indicates that postmastectomy radiotherapy (PMRT) reduces locoregional recurrence (LRR) and improves breast cancer survival in TNBC. Previous reports creatively divided TNBC into four molecular subtypes for personalized treatment. The present study aims to elucidate patterns of LRR in different subtypes of TNBC after PMRT. Methods: From 2019 to 2022, data from 349 AJCC 7th edition stage II-III breast cancer patients treated with mastectomy and PMRT were retrospectively analyzed. These patients were classified into the basal-like immune-suppressed (BLIS) and non-BLIS groups based on the immunohistochemistry biomarkers. The cumulative incidence function was applied to estimated LRR rates, with death as a competing risk, using Gray's test for comparisons. Results: According to the IHC results, a total of 255 patients belonged to the non-BLIS group and 94 to the BLIS group. The 3-year LRR for the entire cohort was 5.16%. There were 9 cases each in the non-BLIS subtype (3.5%) and BLIS subtype (9.6%). The cumulative incidence of LRR between the two groups was significantly different, with a rate of 4.0% in the non-BLIS group and 9.0% in the BLIS group ( P = 0.02). Among the 18 patients with LRR in the whole population, 11 had isolated LRR and 7 were diagnosed with LRR with concurrent distant metastases. The most common area of recurrence in both subtypes was the supraclavicular region. The majority of recurrences occurred within the RT field (in-field), and no isolated out-of-field relapse was observed. In multivariate analysis, independent factors predicting higher LRR were the BLIS subtype (HR = 3.06, P = 0.02). Conclusions: Study results suggest that TNBC of the BLIS subtype is at higher risk for LRR. Immunohistochemistry-based molecular typing may serve as a prognostic biomarker to guide postmastectomy radiotherapy in patients with TNBC. New strategies are needed to improve local control rates in patients with BLIS subtype.

The impact of bolus on clinical outcomes for post-mastectomy breast cancer patients treated with IMRT: data from China

PurposeThis study aims to investigate the effects of chest wall bolus in intensity-modulated radiotherapy (IMRT) technology on clinical outcomes for post-mastectomy breast cancer patients.Materials and methodsThis retrospective study included patients with invasive carcinoma ((y)pT0-4, (y)pN0-3) who received photon IMRT after mastectomy at the Affiliated Hospital of Qingdao University from 2014 to 2019. The patients were divided into two groups based on whether they received daily bolus application or not, and the baseline characteristics were matched using propensity score matching (PSM). Cumulative incidence (CI) of local recurrence (LR), locoregional recurrence (LRR), overall survival (OS) and disease-free survival (DFS) were evaluated with a log-rank test. Acute skin toxicity and late radiation pneumonia was analyzed using chi-square test.ResultsA total of 529 patients were included in this study, among whom 254 (48%) patients received bolus application. The median follow-up time was 60 months. After matching, 175 well-paired patients were selected. The adjusted 5-year outcomes (95% confidence interval) in patients treated with and without bolus were, respectively: CI of LR 2.42% (0.04–4.74) versus 2.38% (0.05–4.65), CI of LRR 2.42% (0.04–4.74) versus 3.59% (0.73–6.37), DFS 88.12% (83.35–93.18) versus 84.69% (79.42–90.30), OS 94.21% (90.79–97.76) versus 95.86% (92.91–98.91). No correlation between bolus application and skin toxicity (P = 0.555) and late pneumonia (P = 0.333) was observed.ConclusionsThe study revealed a low recurrence rate using IMRT technology. The daily used 5 mm chest wall bolus was not associated with improved clinical outcomes.

Impact of LKB1 status on radiation outcome in patients with stage III non-small-cell lung cancer

Preclinical studies suggest that loss of LKB1 expression renders cancer cells less responsive to radiation partly through NRF2-mediated upregulation of antioxidant enzymes protecting against radiation-induced DNA damage. Here we investigated the association of an alteration in this pathway with radio-resistance in lung cancer patients. Patients with locally advanced non-small cell lung cancer (LA-NSCLC) who were treated with chemoradiotherapy (CRT) and analyzed for LKB1 expression using semiquantitative immunohistochemistry. Clinical characteristics and expression of LKB1 were analyzed for association with radiotherapy outcomes. We analyzed 74 available tumor specimens from 178 patients. After a median follow-up of 40.7 months, 2-year cumulative incidence of locoregional recurrence (LRR) in patients who had LKB1Low expression was significantly higher than those with LKB1High expression (68.8% vs. 31.3%, P = 0.0001). LKB1Low expression was found significantly associated with a higher incidence of distant metastases (DM) (P = 0.0008), shorter disease-free survival (DFS) (P = 0.006), and worse overall survival (OS) (P = 0.02) compared to LKB1High expression. Moreover, patients with LKB1Low expression showed a significantly higher 2-year cumulative incidence of LRR (77.6% vs. 21%; P = 0.02), higher DM recurrence (P = 0.002), and shorter OS (P < 0.0001) compared with the EGFR-mutant group. For all patients with LKB1Low who had LRR, these recurrences occurred within the field of radiation, in contrast to those with LKB1High expression having both in-field, marginal, and out-of-field failures. LKB1 expression may serve as a potential biomarker for poor outcomes after receiving radiation in LA-NSCLC patients. Further studies to confirm the association and application are warranted.

Radiotherapy Use and Incidence of Locoregional Recurrence in Patients With Favorable-Risk, Node-Positive Breast Cancer Enrolled in the SWOG S1007 Trial

Little is known about regional nodal irradiation (RNI) practice patterns or rates of locoregional recurrence (LRR) with and without RNI in patients with limited nodal disease and favorable biology treated with modern surgical and systemic therapy, including approaches that de-escalate those latter treatments. To investigate how often patients with low-recurrence score breast cancer with 1 to 3 nodes involved receive RNI, incidence and predictors of LRR, and associations between locoregional therapy and disease-free survival. In this secondary analysis of the SWOG S1007 trial, patients with hormone receptor-positive, ERBB2-negative breast cancer, and a Oncotype DX 21-gene Breast Recurrence Score assay result of no more than 25, were randomized to endocrine therapy alone vs chemotherapy then endocrine therapy. Prospectively collected radiotherapy information was collected from 4871 patients treated in diverse settings. Data were analyzed June 2022 to April 2023. Receipt of RNI (targeting at least the supraclavicular region). Cumulative incidence of LRR was calculated by locoregional treatment received. Analyses were assessed for associations between invasive disease-free survival (IDFS) and locoregional therapy, adjusted for menopausal status, treatment group, recurrence score, tumor size, nodes involved, and axillary surgery. Radiotherapy information was recorded in the first year after randomization, so survival analyses were landmarked as starting at 1 year among those still at risk. Of 4871 female patients (median [range] age, 57 [18-87] years) with radiotherapy forms, 3947 (81.0%) reported radiotherapy receipt. Of 3852 patients who received radiotherapy and had complete information on targets, 2274 (59.0%) received RNI. With a median follow-up of 6.1 years, the cumulative incidence of LRR by 5 years was 0.85% among patients who received breast-conserving surgery and radiotherapy with RNI; 0.55% after breast-conserving surgery with radiotherapy without RNI; 0.11% after mastectomy with postmastectomy radiotherapy; and 1.7% after mastectomy without radiotherapy. Similarly low LRR was observed within the group assigned to endocrine therapy without chemotherapy. The rate of IDFS did not differ by RNI receipt (premenopausal: hazard ratio [HR], 1.03; 95% CI, 0.74-1.43; P = .87; postmenopausal: HR, 0.85; 95% CI, 0.68-1.07; P = .16). In this secondary analysis of a clinical trial, RNI use was divided in the setting of biologically favorable N1 disease, and rates of LRR were low even in patients who did not receive RNI. Disease-free survival was not associated with RNI receipt; omission of chemotherapy among patients similar to those enrolled in the S1007 trial is not an independent indication for use of RNI.

Locally Advanced, pT4 Well-Differentiated Thyroid Cancer in Young Patients – A Population-Based Study

<h3>Purpose/Objective(s)</h3> Locally advanced, non-metastatic pT4 well-differentiated thyroid cancer (WDTC) diagnosed at age <55 years is considered to be Stage I disease by the American Joint Committee on Cancer (AJCC) 8^th edition staging system implying excellent cause-specific survival (CSS) outcomes of ≥95% at 10 years. There are no published outcomes however on this specific cohort of patients, and they may be underrepresented in published outcome series as they comprise of <5% of all WDTC patients. Thus, the objective was to determine the recurrence and survival outcomes of this cohort. <h3>Materials/Methods</h3> We conducted a population-based retrospective study of all patients with pT4 WDTC diagnosed at age <55 years, treated in our province from 1985 to 2013 were extracted. Demographic and treatment factors were extracted. The primary endpoints were cumulative incidence of locoregional recurrence (LRR), cause-specific survival (CSS) and overall survival (OS). Competing risk Fine-Grays analysis and Cox-proportional hazards model was used. <h3>Results</h3> There were 218 patients (median follow up 18.2 years) with 137 under the age of 45. Patients were all treated with thyroidectomy. Most patients had papillary histology (95.9%). Adjuvant radioactive iodine was administered in 88% of cases, and 43% received adjuvant external-beam radiotherapy (EBRT). The 15-year LRR was 21%. On multivariate analysis, there was a trend towards EBRT receipt and lower LRR (HR:0.47, p=0.06). Of the patients who did not receive EBRT, but had a LRR (n=19), 11 were salvaged (with RAI, EBRT, and surgery) and only two died of WDTC (both from LRR). For the cohort as a whole, the 15-year CSS was 96%. There were four deaths secondary to LRR and seven deaths from distant disease. Advanced age, larger tumor size, higher T stage, and presence of LVI were associated with worse CSS (all p<0.05), though we note the limited number of events limit the conclusions from our multivariate analysis. The 15-year OS was 93%. Older age, tumor size, and lymphovascular invasion were significantly associated with worse OS (all p<0.05). On multivariate analysis, EBRT receipt was not associated with improved CSS or OS. <h3>Conclusion</h3> Despite very locally advanced disease, patients with non-metastatic pT4 WDTC, <55 years at diagnosis, have favorable long-term outcomes. Further prospective studies of adjuvant EBRT are needed in this population.

Effect of Postmastectomy Radiotherapy in Breast Cancer Patients according to Pathologic Nodal Status and Molecular Subtype after Neoadjuvant Chemotherapy

<h3>Purpose/Objective(s)</h3> The role of post-mastectomy radiation therapy (PMRT) in breast cancer patients who have achieved ypN0 after neoadjuvant chemotherapy (NAC) has not yet been established. This study aimed to evaluate the benefit of PMRT according to pathologic node status and molecular subtype in breast cancer patients who were treated NAC. <h3>Materials/Methods</h3> We retrospectively reviewed 511 patients with clinical stage II-III breast cancer who underwent NAC and mastectomy at our institution from 2013 to 2017. After mastectomy, ypN+ and ypN0 were identified in 289 (56.6%) and 222 (43.4%), respectively. In this study, molecular subtypes were classified according to hormone receptor (HR) and HER2 receptors as follows: luminal (HR+/HER2-), luminal-HER2 (HR+/HER2+), HER2 enriched (HR-/HER2+), triple-negative (HR -/HER2-). All HER2-positive patients were treated with trastuzumab-containing NAC. Of the total patients, 448 (87.7%) received PMRT and 63 (12.3%) did not. In ypN+ patients, PMRT was performed in 265 (91.7%) and 24 (8.3%) did not. In ypN0 patients, PMRT was performed in 183 (82.4%) and 39 (17.6%) did not. The effect of PMRT on locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival (OS) was evaluated based on pathologic nodal status and molecular subtypes. <h3>Results</h3> The median follow-up duration was 58 months. The cumulative incidence of locoregional recurrence and distant metastasis were 11.8% and 31.5% in ypN+ patients, and 6.8% and 13.5% in ypN0 patients, respectively. In ypN+ patients, PMRT showed significant benefit for LRRFS, DFS, and OS in multivariate analysis (all P < 0.001). In ypN0 patients, triple-negative subtype and lymphovascular invasion were significant prognostic factors for LRRFS (all P < 0.001) and DFS (P = 0.002 and P < 0.001, respectively) by multivariate analysis. However, in ypN0 patients, PMRT was not significantly associated with LRRFS, DFS, and OS. In addition, PMRT showed no significant difference in LRRFS in all molecular subtypes of ypN0 patients. <h3>Conclusion</h3> PMRT should be performed in patients with residual lymph node following NAC and mastectomy. Although a limited number of patients, this study suggests that the role of PMRT in ypN0 patients regardless of subtype remains unclear.

OPTimizing Irradiation through Molecular Assessment of Lymph node (OPTIMAL): a randomized clinical trial

Background and purposeIn breast cancer (BC) patients, the involvement of four or more lymph nodes (LN) is an indication of regional irradiation. The optimal treatment strategy remains unclear when fewer nodes are involved and lymphadenectomy is not performed. We designed a clinical trial to show the non-inferiority of Incidental (INC) compared to intentional (INT) irradiation of axillary nodes in patients with early-stage BC and low burden LN involvement. Materials and methodsBC patients, cN0 (n = 487) undergoing breast conservation surgery and sentinel node biopsy, with total tumor load assessed by OSNA (One-Step Nucleic Acid Amplification) of 250–15,000 copies mRNA CK19/µL in sentinel LN were randomized to receive INC or INT nodal irradiation. The primary endpoint was 5-year disease-free survival (DFS). Secondary endpoints were locoregional recurrence (LRR), distant recurrence (DR), and acute and chronic toxicity (CT). ResultsFive-years DFS were 93.7% (INC) and 93.8% (INT) (difference 0.1% [one-sided 95% CI < 5.7%]; non-inferiority p = 0.075). Cumulative Incidences of LRR were 3.5% (INC) and 3.4% (INT) (difference of 0.1% [<4.8%]; p = 0.021), and 5% (INC) and 3.5% (INT) (difference 1.4% [<6.0%]; non-inferiority p = 0.101) for DR. CT was more Incident with INT (26.9%) than with INC (19.2%), though the difference was not statistically significant (HR 1.39 [95% CI: 0.92, 2.10]; p = 0.11). ConclusionIntentional does not outperform incidental irradiation by more than 5.7% in terms of 5-year DFS, 4.8% for LRR, and 6% for DR.Registration Number: ClinicalTrials.gov Identifier: NCT02335957.

A Single-Center Retrospective Analysis of Local and Distant Relapse of Breast Cancer Following Immediate Breast Reconstruction According to Molecular Subtypes.

PurposeConcerns have been raised about the oncologic safety of immediate breast reconstruction (IBR) following mastectomy for breast cancer. This study aimed to evaluate locoregional recurrence (LRR) and distant metastasis (DM) of breast cancer according to its molecular subtype in patients who underwent mastectomy alone or IBR after mastectomy.MethodsIn this retrospective cohort study, consecutive breast cancer patients treated by the single senior surgeon (XZ) between February 2010 and December 2014 were eligible. In total, 389 consecutive patients were included; 295 patients underwent mastectomy alone and 94 patients underwent mastectomy with IBR. Data were retrospectively collected and analyzed for LRR and DM stratified by molecular subtypes.ResultsWith a median follow-up of 73 and 87.5 months, 1.69% of patients in the mastectomy alone group developed LRR compared to 0% in the reconstruction group (p = 0.342) and the total incidence of DMs was 11.52% in patients who received mastectomy alone and 7.44% in patients who received postmastectomy IBR (p = 0.262), respectively. The cumulative incidence of LRR was 2.1% vs. 0% for luminal A, 0% vs. 0% for luminal B, 0% vs. 0% for human epidermal growth factor receptor 2 (HER2)-enriched, and 4.5% vs. 0% for triple-negative in the mastectomy alone group compared to the postmastectomy IBR group. The cumulative incidence of DM was 15.5% vs. 5.7% for luminal A, 10% vs. 8.7% for luminal B, 17.3% vs. 0% for HER2-enriched, and 6.8% vs. 7.1% for triple-negative in the mastectomy alone group compared to the postmastectomy IBR group. On multivariable Cox regression analysis, lymph node metastasis was associated with an increased risk of DM in the mastectomy alone group (p = 0.03) and neoadjuvant chemotherapy was associated with an increased risk of DM in the postmastectomy IBR group (p = 0.021).ConclusionThis study suggests that IBR does not have a negative impact on the LRR and DM of breast cancer according to molecular subtypes.

Postmastectomy radiotherapy in high-risk breast cancer patients given adjuvant systemic therapy. A 30-year long-term report from the Danish breast cancer cooperative group DBCG 82bc trial

BackgroundBetween 1982 and 1990 the Danish Breast Cancer Cooperative Group (DBCG) conducted a randomized trial in high-risk pre- and postmenopausal (<70 years) breast cancer patients comparing mastectomy plus adjuvant systemic therapy alone versus the same treatment plus postoperative irradiation. AimTo present a comprehensive analysis of the complete DBCG 82bc study with a 30-year long-term follow-up of the cancer therapeutic effect and survival, together with an additional focus on the potential long-term life-threatening morbidity related to cardiac irradiation and/or the risk of secondary cancer induction. MethodsA total of 3083 patients with pathological stage II and stage III breast cancer were after mastectomy randomly assigned to receive adjuvant systemic therapy and postoperative irradiation to the chestwall and regional lymph nodes (1538 pts), or adjuvant systemic therapy alone (1545 pts). Pre- and menopausal patients (DBCG 82b) received 8–9 cycles of CMF with an interval of 4 weeks, whereas postmenopausal patients (DBCG 82c) received tamoxifen 30 mg daily for one year. The median follow-up time was 34 years. The primary endpoints were loco-regional recurrence (LRR) and overall mortality, and the secondary endpoints were distant metastasis, breast cancer mortality, and irradiation related late morbidity. ResultsOverall the 30-year cumulative incidence of loco-regional recurrence was 9% in irradiated patients versus 37% in non-irradiated patients who received adjuvant systemic therapy alone (HR: 0.21 [95% cfl 0.18–0.26]). Distant metastasis probability at 30 years was 49% in irradiated patients compared to 60% in non-irradiated (HR: 0.77 [0.70–0.84]). Consequently, these figures resulted in a reduced breast cancer mortality: 56% vs 67% (HR: 0.75 [0.69–0.82], and overall mortality (81% vs 86% at 30 years (p < 0.0001), HR: 0.83 [0.77–0.90] in favor of irradiation. Radiotherapy did not result in any significant excess death of other courses, such as ischemic heart disease, HR: 0.82 [0.58–1.18]; nor secondary lung cancer HR: 1.44 [0.92–2.24], or other non-cancer related death HR: 1.15 [0.92–1.45]. ConclusionThe study definitely demonstrate that optimal long-term treatment benefit of high-risk breast cancer can only be achieved if both loco-regional and systemic tumor control are aimed for. Therefore, radiotherapy has an important role in the multidisciplinary treatment of breast cancer. The PMRT treatment did not result in excess ischemic heart damage, nor in other non-breast cancer related death.

Outcome without any adjuvant systemic treatment in stage I ER+/HER2− breast cancer patients included in the MINDACT trial

Adjuvant systemic treatments (AST) reduce mortality, but have associated short- and long-term toxicities. Careful selection of patients likely to benefit from AST is needed. We evaluated outcome of low-risk breast cancer patients of the EORTC 10041/BIG 3-04 MINDACT trial who received no AST.Patients with estrogen receptor-positive, HER2-negative, lymph node-negative tumors ≤2 cm who received no AST were matched 1 : 1 to patients with similar tumor characteristics treated with adjuvant endocrine therapy (ET), using propensity score matching and exact matching on age, genomic risk (70-gene signature) and grade. In a post hoc analysis, distant metastasis-free interval (DMFI) and overall survival (OS) were assessed by Kaplan-Meier analysis and hazard ratios (HR) by Cox regression. Cumulative incidences of locoregional recurrence (LRR) and contralateral breast cancer (CBC) were assessed with competing risk analyses.At 8 years, DMFI rates were 94.8% [95% confidence interval (CI) 92.7% to 96.9%] in 509 patients receiving no AST, and 97.3% (95% CI 95.8% to 98.8%) in 509 matched patients who received only ET [absolute difference: 2.5%, HR 0.56 (95% CI 0.30-1.03)]. No statistically significant difference was seen in 8-year OS rates, 95.4% (95% CI 93.5% to 97.4%) in patients receiving no AST and 95.6% (95% CI 93.8% to 97.5%) in patients receiving only ET [absolute difference: 0.2%, HR 0.86 (95% CI 0.53-1.41)]. Cumulative incidence rates of LRR and CBC were 4.7% (95% CI 3.0% to 7.0%) and 4.6% (95% CI 2.9% to 6.9%) in patients receiving no AST versus 1.4% (95% CI 0.6% to 2.9%) and 1.5% (95% CI 0.6% to 3.1%) in patients receiving only ET.In patients with stage I low-risk breast cancer, the effect of ET on DMFI was limited, but overall significantly fewer breast cancer events were observed in patients who received ET, after the relatively short follow-up of 8 years. These benefits and side-effects of ET should be discussed with all patients, even those at a very low risk of distant metastasis.

Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy for Patients With Locally Advanced Rectal Cancer

Total neoadjuvant therapy has been increasingly adopted for multimodal rectal cancer treatment. The optimal sequence of chemoradiotherapy (CRT) and chemotherapy needs to be established. To report the long-term results of the secondary end points prespecified in the Randomized Phase 2 Trial of Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy (CAO/ARO/AIO-12 trial) for Locally Advanced Rectal Cancer. This secondary analysis of a randomized clinical trial included 311 patients who were recruited from the accrued CAO/ARO/AIO-12 trial population from June 15, 2015, to January 31, 2018, from 18 centers in Germany. Patients with cT3-4 and/or node-positive rectal adenocarcinoma were included in the analysis. Data were analyzed from June 15, 2015, to January 31, 2018. The follow-up analysis was conducted between January 31, 2018, and November 30, 2020. Patients were randomly assigned to group A for 3 cycles of fluorouracil, leucovorin, and oxaliplatin before fluorouracil/oxaliplatin CRT (50.4 Gy), or to group B for CRT before chemotherapy. Total mesorectal excision was scheduled on day 123 after the start of total neoadjuvant therapy in both groups. The end points assessed in this secondary analysis included long-term oncologic outcomes, chronic toxicity, patient-reported outcome measures for global health status (GHS) and quality of life (QoL), and the Wexner stool incontinence score. Of the 311 patients enrolled, 306 were evaluable, including 156 in group A (mean [SD] age, 60 [11] years; 106 men [68%]) and 150 in group B (mean [SD] age, 62 [10] years; 100 men [67%]). After a median follow-up of 43 months (range, 35-60 months), the 3-year disease-free survival was 73% in both groups (hazard ratio, 0.95; 95% CI, 0.63-1.45, P = .82); the 3-year cumulative incidence of locoregional recurrence (6% vs 5%, P = .67) and distant metastases (18% vs 16%, P = .52) were not significantly different. Chronic toxicity grade 3 to 4 occurred in 10 of 85 patients (11.8%) in group A and 8 of 66 patients (9.9%) in group B at 3 years. The GHS/QoL score decreased after total mesorectal excision but returned to pretreatment levels 1 year after randomization with no difference between the groups. Stool incontinence deteriorated 1 year after randomization in both groups and only improved slightly at 3 years, but never reached baseline levels. This secondary analysis of a randomized clinical trial showed that CRT followed by chemotherapy resulted in higher pathological complete response without compromising disease-free survival, toxicity, QoL, or stool incontinence and is thus proposed as the preferred total neoadjuvant therapy sequence if organ preservation is a priority. ClinicalTrials.gov identifier: NCT02363374.

External Beam Radiation Therapy in pT4 Well-Differentiated Thyroid Cancer: A Population-Based Study of 405 Patients.

The benefit of external beam radiation therapy (EBRT) in locally advanced, well- differentiated thyroid cancer (WDTC) is uncertain. The purpose of this study is to evaluate locoregional recurrence (LRR), progression-free survival, and cause-specific survival (CSS) of patients with pT4 well-differentiated thyroid carcinoma. A population-based retrospective review was conducted of consecutive patients with pT4 WDTC (per the American Joint Committee on Cancer, 8th edition, criteria) treated provincially between 1985 and 2013. The primary endpoints were cumulative incidence of LRR and CSS. To account for the competing risks of death from other causes, a Fine-Gray's test was used. A Cox-proportional hazards model was used to analyze overall survival (OS). Multivariate models and propensity matching were used to account for the effects of covariates. A total of 405 patients were identified with a median follow-up time of 14.3 years for a total of 4209 person-years of follow up. The median age at the time of diagnosis was 53 years (range, 20-87). There were 211 patients (52%) who received EBRT. EBRT was associated with age ≥55 years (56% vs 35%; P < .001), airway involvement (42% vs 8%; P < .001), and R1/2 resection (81% vs 51%; P < .001). The 10-year outcomes for the non-EBRT and EBRT groups were 21.6% versus 11.4%, respectively, for LRR, 84.1% versus 93.1%, respectively, for CSS, and 85.7% versus 67.5%, respectively, for OS. On multivariate analysis, EBRT was associated with a lower rate of LRR (hazard ratio [HR]: 0.334; P < .001), but not associated with CSS (HR: 1.56; P=.142) nor OS (HR: 1.216; P=.335). After propensity score matching, the EBRT cohort had lower rates of LRR relative to the non-EBRT cohort (HR: 0.261; P=.0003), but there were no differences in CSS or OS. In this large, population-based analysis of patients with pT4 WDTC, EBRT was associated with lower rates of LRR, but no difference in CSS or OS.

Updated Outcomes of Split Course Radiotherapy in Elderly or Infirm Patients With Advanced Cancers of the Head and Neck.

Head and neck cancers are often treated with extended courses of radiotherapy (RT), which may prove excessively toxic for frail patients. Split course RT (SCRT) delivers two courses of RT separated by 4-6 weeks, personalizing treatment intensity based on response. In this study, we present our updated experience using this technique. From a single institution database, we identified patients considered for SCRT. For patients undergoing a second course of RT, cumulative incidence of locoregional recurrence (LRR) and overall survival (OS) are reported. A total of 98 patients were included, of whom seventy-five percent underwent a second course of RT. The most common fractionation was 30 Gy in 10 fractions for each course, with a median cumulative dose of 60 Gy. In those undergoing a second course of RT, median OS was 9.7 months and cumulative incidence of LRR at 6, 12, and 24 months was 17.0%, 23.1%, and 29.4%, respectively. SCRT offers an attractive treatment paradigm to personalize radiation intensity based on patient tolerance, while maintaining reasonable safety and efficacy in those unfit for standard full course RT.

Locoregional recurrence via mucus-mediated extension following lung resection for mucinous tumors

BackgroundClinically, locoregional recurrences following mucinous tumor resection are often experienced. However, it remains unclear whether mucinous tumors directly affect local recurrence or not, and if so, the mechanism is not known. Therefore, we investigated whether mucinous tumors are associated with locoregional recurrence after pulmonary resection and whether mucus extension is a risk factor for locoregional recurrence.MethodsThe data of 152 patients who underwent pulmonary resection for metastases were reviewed. When mucus was partially or wholly present in the tumor based on macro- or microscopic identification, we assigned the tumor as mucinous. In mucinous tumors, when mucus was identified within the air spaces in the normal lung parenchyma, beyond the edge of the tumor, we assigned the tumor as positive for “mucus extension.”ResultsThe 5-year cumulative incidence of locoregional recurrence in patients with mucinous tumors was 48.1%, which was significantly higher than that observed in those with non-mucinous tumors (14.9%). Within the mucinous tumor, the presence of mucus extension beyond the tumor edge was an independent risk factor for locoregional recurrence after pulmonary resection (hazard ratio, 5.52; P = 0.019).ConclusionsDuring the resection of mucinous cancer, surgeons should maintain sufficient distance from the tumor edge to prevent locoregional recurrences.

Prognostic effect of perineural invasion in surgically treated esophageal squamous cell carcinoma.

BackgroundAlthough perineural invasion is a well known prognostic factor used in several cancers, its prognostic role in esophageal squamous cell carcinoma remains controversial. Here, we investigated the prognostic role of perineural invasion in surgically treated esophageal squamous cell carcinoma.MethodsWe retrospectively reviewed the medical records of 316 patients who underwent esophagectomy and lymph node dissection for esophageal squamous cell carcinoma between 2007 and 2016.ResultsOverall, 287 men (mean age: 62.73 ± 7.97 years) were included in the study. The median follow‐up period was 35.97 ± 30.99 months, perineural invasion was confirmed in 25 patients, and three‐year overall and disease‐free survival were significantly lower in the perineural invasion group than in the no‐perineural invasion group (75.9% vs. 40.0%, p < 0.001; 70.3% vs. 21.6%, p < 0.001). Cumulative incidences of locoregional recurrence and distant metastasis over three years were higher in the perineural invasion group (13.8% vs. 9.6%, p = 0.009 and 52.8% vs. 14.6%, p < 0.001). On performing multivariable analysis, perineural invasion, pathological stage, incomplete resection, and neoadjuvant therapy were adverse risk factors for disease‐free survival. The concordance index increased when perineural invasion was included in the model (0.712 vs. 0.723). On subgroup analysis, perineural invasion demonstrated a prognostic value in node‐negative patients (79.4% vs. 35.7%, p = 0.012).ConclusionsPerineural invasion was found to be an adverse risk factor for disease‐free survival in surgically treated patients with esophageal squamous cell carcinoma. Close observation and individualized adjuvant therapy may be helpful for patients with perineural invasion.

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.

Clinical Effectiveness of an Adaptive Treatment Planning Algorithm for Intensity Modulated Radiation Therapy Versus 3D Conformal Radiation Therapy for Node-Positive Breast Cancer Patients Undergoing Regional Nodal Irradiation/Postmastectomy Radiation Therapy

Clinical trials support adjuvant regional nodal irradiation (RNI) after breast-conserving surgery or mastectomy for patients with lymph node-positive breast cancer. Advanced treatment planning techniques (eg, intensity modulated radiation therapy [IMRT]) can reduce dose to organs at risk (OARs) in this situation. However, uncertainty persists about when IMRT is clinically indicated (vs 3-dimensional conformal radiation therapy [3DCRT]) for RNI. We hypothesized that an adaptive treatment planning algorithm (TPA) for IMRT adoption would allow OAR constraints for RNI to be met when 3DCRT could not without significantly changing toxicity and locoregional recurrence (LRR) patterns. Since 2013, all RNI patients also underwent an adaptive TPA that began with 3DCRT and then changed to IMRT when OAR constraints (mean heart dose ≤500 cGy; ipsilateral lung V20 ≤35%) could not be met. Patients received 2 Gy/d to the prospectively contoured target volumes (including internal mammary nodes). We retrospectively evaluated the dosimetry and clinical outcomes of the treatment groups (IMRT vs 3DCRT). The primary endpoint was the cumulative incidence of LRR as the site of first recurrence, and we specifically address patterns of failure based on dose to the posterior supraclavicular nodal region (SCL-post). Two hundred forty patients (60% stage III; mean 4.0 + nodes) underwent an adaptive-TPA for RNI after mastectomy (74%) or breast-conserving surgery (26%), resulting in 168 patients treated with 3DCRT and 72 patients treated with IMRT. There were 7 LRRs (2 IMRT, 5 3DCRT) resulting in 4-year LRR of 2.8% for IMRT versus 1.8% for 3DCRT (P = .99). Three patients (2 IMRT, 1 3DCRT) had SCL nodal failures (1 in the SCL-post). An adaptive TPA for use of IMRT when 3DCRT does not meet critical OAR constraints resulted in rare high-grade toxicity and no difference in failure patterns between patients treated with IMRT and 3DCRT. These data should provide reassurance that IMRT maintains the therapeutic ratio by preserving cancer control outcomes without excess toxicity when 3DCRT fails to meet OAR constraints.

Oncologic safety of immediate autologous fat grafting for reconstruction in breast-conserving surgery.

Autologous fat grafting (AFG), or lipofilling, has been used for immediate reconstruction at the time of breast-conserving surgery in order to achieve a satisfactory cosmetic outcome in patients with breast cancer and an unfavorable tumor-to-breast volume ratio or unfavorable tumor location. However, the oncologic safety of this technique is still unclear. To determine whether AFG performed simultaneously with breast-conserving surgery is associated with differences in local relapse rates and disease-free survival. Matched retrospective cohort study. Tertiary referral center. Patients undergoing breast-conserving surgery with or without AFG between 2004 and 2016 were retrospectively enrolled and matched for age, staging, grade, tumor histology, and tumor immunohistochemical profile. The cumulative incidence of locoregional recurrence (LRR) and disease-free survival were the primary end points, while distant recurrence and overall survival were the secondary end points. A total of 320 patients were followed. Cases were matched with controls at a 1:4 ratio. There was no difference in LRR or distant recurrence of breast cancer between the two groups. The annual LRR rate was 0.86% in patients who received immediate AFG vs. 0.7% in patients undergoing breast-conserving surgery alone (p ≥ 0.05). Number of lymph nodes was the sole independent risk factor for local recurrence (p = 0.045). No significant differences in disease-free survival rates were found between the groups. At a mean follow-up of 5years, no significant differences in locoregional recurrence rates were found between patients who received immediate AFG and those who underwent breast-conserving surgery alone. These findings corroborate previous research demonstrating the oncological safety of immediate AFG reconstruction, further suggesting that this technique as a safe, effective way to achieve optimal cosmetic outcomes in primary breast cancer surgery without jeopardizing oncologic outcomes.

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.

Long-Term Oncologic Outcomes After Curative Resection of Familial Medullary Thyroid Carcinoma.

Long-term outcomes after curative resection in patients with germline RET mutations and medullary thyroid cancer (MTC) are highly variable and mutation-specific oncologic outcomes are not well-described. Sixty-six patients identified from 1986 to 2017 from a single-institution cancer database were assessed for recurrence and survival using Kaplan-Meier estimates, and correlated with clinicopathologic features using log-rank or Cox proportional hazards. Median follow-up was 9.3years (range 0.3-31.5), median tumor diameter was 1.5cm (range 0.1-7.5), and preoperative calcitonin was known in 41 patients [median 636 (range 0-9600)]. Overall survival (OS) of the cohort was 94% at 10years, the cumulative incidence of locoregional recurrence was 38% at 10years, and 19/24 (79%) patients underwent repeat neck operation. The cumulative incidence of distant recurrence was 27% at 10years. Predictors of distant recurrence were tumor size, positive lymph nodes, and pre- and postoperative carcinoembryonic antigen, but not calcitonin. M918T mutation-bearing patients had 10-year distant recurrence-free survival of 0%, compared with 83% in all other patients (p < 0.001), and equivalent 10-year OS (100% vs. 92%; p = 0.49). Structural and metastatic recurrence is common in patients with germline RET mutations, and MTC and can occur 20years after initial treatment, however survival remains high. Management should focus on optimal surveillance strategies and long-term control of structural disease.