Distant Disease-free Survival Rates Research Articles

Abstract PO5-22-08: Comparison of long-term oncological outcomes in young women with breast cancer between BRCA-mutation carriers versus non-carriers: How genetic risk factors and tumor characteristics influence the prognosis

Abstract Objectives and rationale: Breast cancer (BC) arising at a young age is relatively uncommon; however, approximately 6 to 10% of women diagnosed with BC are younger than the age 40. This subgroup of young women presents different risk factors, tumor biology, and clinical outcomes. Moreover, the interpretation of the effects of inherited genetic factors on the prognosis of young patients with BC remains a subject of debate. The primary aim of this study was to evaluate the characteristics of young patients with BC and to compare the long-term oncological results between BRCA-mutation carriers and non-carriers. We retrospectively reviewed all the consecutive young (≤ 40 years old) BC patients treated at the Breast Unit of IRCCS Humanitas Research Hospital (Milan, Italy). All young patients underwent BRCA-mutation analysis. For further analysis young BC patients were divided into two groups: BRCA-mutation carriers versus non-carriers. Tumor, surgical treatment, and post-operative data were compared between the two groups. Primary end-points were: disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS). The Kaplan-Meier method was used to generate the recurrence and survival curves. Multivariate analyses were performed using the Cox proportional hazards model to identify independent risk and protective factors for DFS, DDFS, and OS. Results: The characteristics of 63 young BC patients with BRCA-mutation were compared with 339 young BC patients without BRCA-mutation. BRCA-mutation carriers tend to be younger (60.3% versus 34.8% if age ≤ 35 years, odds ratio (OR) = 17.699, 95% confidence interval (95%CI) = 33.871-35.568, p = 0.001) and present more aggressive tumors (66.7% versus 40.7% if G3, OR = 17.119, 95%CI = 2.549-2.828, p = 0.001; 57.2% versus 12.4% if biological subtype triple negative, OR = 52.727, 95%CI = 2.042-2.417, p = 0.001; 73.0% versus 39.2% if Ki67 ≥ 25%, OR = 58.981, 95%CI = 47.135-58.505, p = 0.001). Young BC patients without BRCA-mutation presented significantly better long-term oncological results in terms of DFS, DDFS, and OS compared with young BRCA-mutation carriers (10-years DFS rate 91.1% versus 58.1%, p < 0.001; 10-year DDFS rate 91.2% versus 76.1%, p = 0.003; 10-year OS rate 98.0% versus 87.8%, p = 0.002, respectively). Neo-adjuvant chemotherapy was found to be an independent protective factor for OS in young BRCA-mutated BC patients (hazard radio = 14.885, 95%CI = 2.343-94.566, p = 0.004). Conclusions: Breast cancer is more likely to present at a younger age (≤ 35 years) and with more aggressive characteristics (G3, triple negative, Ki67 ≥ 25%) in patients with BRCA-mutation compared with their non-mutated counterpart. Young BRCA-mutation carriers show a poorer prognosis in terms of recurrence and survival compared with non-carriers. The implementation of neo-adjuvant chemotherapy may improve survival in young BC patients with BRCA-mutation. Citation Format: Damiano Gentile, Simone Di Maria Grimaldi, Andrea Sagona, Erika Barbieri, Alberto Bottini, Giuseppe Canavese, Giulia Caraceni, Shadya Darwish, Corrado Tinterri. Comparison of long-term oncological outcomes in young women with breast cancer between BRCA-mutation carriers versus non-carriers: How genetic risk factors and tumor characteristics influence the prognosis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-22-08.

Risk factors for late recurrence and postrelapse survival in estrogen receptor (ER)-positive, human epidermal growth factor receptor (HER) 2-negative breast cancer after 5 years of endocrine therapy

It is unclear which patients with ER-positive, HER2-negative breast cancer benefit from extended endocrine therapy beyond 5 years. Prognostic factors for late-recurring breast cancer postrelapse survival have been reported. We retrospectively analyzed data from 892 patients with ER-positive and HER2-negative invasive breast cancer who were disease-free after completing a 5-year adjuvant endocrine therapy. Patients were then classified as high-risk (positive lymph nodes, large tumor size, high tumor grade) or low-risk. High-risk patients were divided into extended endocrine therapy and stop groups. Comparisons were made using propensity score matching, and the benefits of extended endocrine therapy for high-risk patients and prognostic factors for postrelapse survival were assessed. The high- and low-risk groups comprised 444 and 448 patients, respectively. The 10-year distant disease-free survival (DDFS) rates were 96.3 % (95 % confidence interval [CI] 0.912–0.985) and 86.5 % (95 % CI 0.798–0911) in the extended and stop groups, respectively (P = 0.00382). Cox proportional hazards model revealed that extended endocrine therapy promoted greater reduction in distant metastasis risk than 5-year endocrine therapy in high-risk populations (hazard ratio [HR] 0.27; 95 % CI 0.11–0.68; P = 0.0054). Postrelapse survival was significantly different in patients with DDFS ≥7 years (HR 0.24; 95 % CI 0.072–0.81; P = 0.021) and those with better response to first-line treatment (HR 0.072; 95 % CI, 0.058–0.90; P = 0.041). Patients with risk factors for late recurrence should be considered for extended endocrine therapy. Longer DDFS and response to first-line treatment may be a prognostic factor for postrelapse survival after late recurrence.

Feasibility of Sentinel Lymph Node Biopsy in Breast Cancer Patients with Axillary Conversion after Neoadjuvant Chemotherapy-A Single-Tertiary Centre Experience and Review of the Literature.

(1) Introduction: Sentinel lymph node biopsy (SLNB) is widely used in breast cancer patients who undergo neoadjuvant chemotherapy (NAC), replacing axillary lymph node dissection. While commonly accepted for cN0 patients, its role in cN1/2 patients remains controversial. Our study aims to investigate the role of SLNB in BC patients who underwent prior NAC and compare our results to those of other studies presented in the literature. (2) Materials and methods: Our retrospective study included 102 breast cancer patients who received NAC before 99mTc-albumin Nanocolloid SLN mapping and SLNB was performed, completed or not with axillary dissection. A review based on the PRISMA statement was also carried out, encompassing 20 studies. (3) Results: The lymphoscintigraphy performed after the administration of NAC presented an identification rate (IR) of 93.13%. IR for SLNB was 94.11%, with a false-negative rate (FNR) of 7.4%. After a median follow-up of 31.3 months, we obtained a distant disease-free survival rate of 98%. The results obtained by other groups were similar to those of our study, presenting IR in the range 80.8-96.8%, with FNR varying from 0 to 22%. (4) Conclusions: on conclusion, SLNB can accurately determine the lymph node status, with an acceptable FNR and maintain its expected prognostic role with low recurrence rates, and our results are comparable to those obtained by other studies.

Oncologic safety of breast conservation following NACT in women with locally advanced breast cancer.

Breast conservation surgery (BCS) is the accepted standard of treatment for early breast cancer, with evidence from randomized controlled and population-based studies. The oncological outcome of BCS in locally advanced breast cancer (LABC) is mainly available from retrospective series with a small sample size and a shorter follow-up duration. A retrospective observational study of 411 non-metastatic LABC patients who received neoadjuvant chemotherapy (NACT) followed by surgery from 2011 to 2016. We retrieved the data from a prospectively maintained database and electronic medical records. Survival data were analyzed by Kaplan-Meier curves and Cox regression using Statistical Package for the Social Sciences 25 and STATA 14. 146/411 (35.5%) women had BCS with a margin positivity rate of 3.42%. With a median follow-up of 64 months (IQR 61, 66), the local relapse rate was 8.9% in BCS and 8.3% after mastectomy. The estimated 5-year locoregional recurrence-free survival (LRFS), recurrence-free survival (RFS), distant disease-free survival (DDFS) and overall survival (OS) rates of BCS were 86.9%, 63.9%, 71% and 79.3%, and 90.1%, 57.9%, 58.3% and 71.5% in the mastectomy group. On univariate analysis, BCS showed superior survival outcomes compared to mastectomy (unadjusted HR (95% CI) for RFS: 0.70 (0.50-1), DDFS: 0.57 (0.39-0.84), OS: 0.58 (0.36-0.93)). After adjusting for age, cT stage, cN stage, poorer chemotherapy response (ypT0/is, N0) and radiotherapy, BCS and mastectomy groups were found comparable in terms of LRFS (HR: 1.1, 0.53-2.3), DDFS (HR: 0.67, 0.45-1.01), RFS (HR: 0.80, 0.55-1.17) and OS (HR: 0.69, 0.41-1.14). BCS is technically feasible in LABC patients. LABC patients who respond well to NACT can be offered BCS without compromising survival outcomes.

Cisplatin-docetaxel induction chemotherapy for patients with nasopharyngeal carcinoma in a non-endemic cohort

This is the report on our clinic’s 15 years of experience (2004–2018) on nasopharyngeal carcinoma (NPC), treated with induction chemotherapy (IC) and subsequent concomitant chemoradiotherapy (CCRT), comprising population characteristics and treatment outcomes of 203 patients with non-metastatic NPC. IC comprised docetaxel (75 mg/m2) and cisplatin (75 mg/m2) combination (TP). Concurrent cisplatin (P) was applied either weekly (40 mg/m2, 32 cases) or every-3-week (100 mg/m2, 171 cases). The median follow-up duration was 85 months (range, 5–204 months). Overall and distant failure rates were observed in 27.1% (n = 55) and 13.8% (n = 28) patients, respectively. The 5-year locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 84.1%, 86.4%, 75%, and 78.7% respectively. The overall stage was an independent prognostic factor for the LRRFS, DMFS, DFS, and OS. The WHO histological type was a prognostic factor for the LRRFS, DFS, and OS. Age was a prognostic factor for the DMFS, DFS, and OS. Concurrent P schedule was independent prognostic only the LRRFS.

Abstract PD9-05: Stromal tumor-infiltrating lymphocytes identify early-stage triple-negative breast cancer patients with favorable outcomes at 10-year follow-up in the absence of systemic therapy: a pooled analysis of 1835 patients

Abstract Background: The prognostic value of stromal tumor-infiltrating lymphocytes (TILs) as a biomarker for triple-negative breast cancer (TNBC) has been extensively demonstrated in patients (pts) receiving (neo)adjuvant systemic therapy. In addition, several small studies suggest that a subset of pts with early-stage TNBC and high TILs have excellent long-term outcomes, even in the absence of systemic therapy [1-3]. However, data on the absolute risk of TNBC recurrence according to TIL levels in the absence of systemic therapy are limited and critical to inform the design of future systemic therapy de-escalation clinical trials. Methods: We conducted an individual patient data pooled analysis of 12 international cohorts of pts with TNBC treated with locoregional therapy but no systemic therapy. TNBC was defined as tumors with estrogen and progesterone receptor of < 1% and HER2 negative (IHC 0, 1+ or IHC 2+ and FISH negative) per local evaluation. TILs were locally assessed in hematoxylin & eosin-stained slides according to the International Immuno-Oncology Biomarker Working Group guidelines (www.tilsinbreastcancer.org). We used the Kaplan-Meier method to assess survival outcomes according to prespecified TIL thresholds: 30% and 50%. Confidence intervals (CI) for survival probabilities were calculated using a percentile bootstrap method. The primary endpoint was invasive disease-free survival (iDFS, STEEP 2.0 definition). Key secondary outcomes included recurrence-free survival (RFS), distant disease-free survival (DDFS) and overall survival (OS). Results: 1,835 pts diagnosed with TNBC between 1982 and 2017 who did not receive systemic therapy were included. The median age at diagnosis was 56 (IQR 38-71). Menopausal status was known in 1,184 women, of whom 78% were post-menopausal. The median tumor size was 2.0 cm (IQR 1.2-2.6). Most pts (87%) had no axillary lymph node involvement (N0). Most tumors were invasive ductal carcinoma (74%) and grade 3 (70%). The median level of TILs was 15% (IQR 5-40). The median duration of follow-up was 30.4 years (95% CI 29.9, 31.1). A total of 950 (52%) iDFS, 828 (45%) RFS, 767 (42%) DDFS events, and 604 (33%) deaths were observed. In multivariable analyses, higher TILs were independently associated with improved iDFS, RFS, DDFS, and OS beyond clinicopathological factors (likelihood ratio p< 10e-6). Each 10% increment in stromal TILs was associated with an 8% (95% CI: 6-11), 10% (95% CI: 7-13), and 13% (95% CI: 10-15) reduction in the risk of experiencing an iDFS, RFS or DDFS event, and with a 12% (95% CI: 9-15) reduction in the risk of death. iDFS, RFS, DDFS and OS rates according to different TIL thresholds and nodal status are shown in the Table. Of note, the RFS estimates (which exclude second non-breast primaries and contralateral breast cancers) were consistently higher than the iDFS counterparts (which include both), consistent with a high rate of contralateral breast cancers and second primary tumors in this cohort. Notably, patients with node-negative—and especially stage I—TNBC with high TILs had excellent survival rates at 10-year follow-up. Conclusion: TILs are highly prognostic in pts with systemically untreated early-stage TNBC. Pts with pN0 (and especially stage I) TNBC with high TILs exhibited very favorable long-term outcomes even in the absence of systemic therapy. These data define the natural history of TIL-rich TNBC pts and are crucial to identifying the optimal patient population for future chemotherapy and immunotherapy de-escalation clinical trials.

Outcomes following open versus laparoscopic multi-visceral resection for locally advanced colorectal cancer: Asystematic review and meta-analysis.

This meta-analysis aims to compare morbidity, mortality, oncological safety, and survival outcomes after laparoscopic multi-visceral resection (MVR) of the locally advanced primary colorectal cancer (CRC) compared with open surgery. A systematic search of multiple electronic data sources was conducted, and all studies comparing laparoscopic and open surgery in patients with locally advanced CRC undergoing MVR were selected. The primary endpoints were peri-operative morbidity and mortality. Secondary endpoints were R0 and R1 resection, local and distant disease recurrence, disease-free survival (DFS), and overall survival (OS) rates. RevMan 5.3 was used for data analysis. Ten comparative observational studies reporting a total of 936 patients undergoing laparoscopic MVR (n = 452) and open surgery (n = 484) were identified. Primary outcome analysis demonstrated a significantly longer operative time in laparoscopic surgery compared with open operations (P = 0.008). However, intra-operative blood loss (P<0.00001) and wound infection (P = 0.05) favoured laparoscopy. Anastomotic leak rate (P = 0.91), intra-abdominal abscess formation (P = 0.40), and mortality rates (P = 0.87) were comparable between the two groups. Moreover the total number of harvested lymph nodes, R0/R1 resections, local/distant disease recurrence, DFS, and OS rates were also comparable between the groups. Although inherent limitations exist with observational studies, the available evidence demonstrates that laparoscopic MVR in locally advanced CRC seems to be a feasible and oncologically safe surgical option in carefully selected cohorts.

Pathological multifocality is not a prognosis factor of papillary thyroid carcinoma: a single-center, retrospective study

IntroductionNon-total thyroidectomy (non-TTx) is a widely accepted operative procedure for low-risk papillary thyroid carcinoma (PTC). PTC patients preoperatively diagnosed with unifocal disease are often revealed as having multifocal foci by microscopy. The present study determined whether or not patients with clinically unifocal, but pathologically multifocal non-high-risk PTC treated with non-TTx have an increased risk of a poor prognosis compared to those with pathologically unifocal PTC.Materials and methodsPTC patients diagnosed as unifocal preoperatively who underwent non-TTx were multifocal in 61 and unifocal in 266 patients microscopically. Oncologic event rates were compared between pathologically multifocal and unifocal PTC patients.ResultsPathological multifocality was associated with positive clinical lymph node metastasis (cN1) (odds ratio [OR] 4.01, 95% confidence interval [CI]: 1.91–8.04) and positive pathological lymph node metastasis (pN1) in > 5 nodes (OR 3.68, 95% CI: 1.60–8.49). No patients died from PTC. There was no significant difference in the disease-free survival rate, remnant thyroid disease-free survival rate, lymph node disease-free survival rate, or distant disease-free survival rate between the two groups. Recurrence in pathologically multifocal PTC patients was locoregional in all cases and able to be salvaged by reoperation. Cox proportional hazard model analyses showed no significant difference in recurrence rates with regard to pathological multifocality and cN or number of pNs.ConclusionThe prognosis of PTC with pathological multifocality treated by non-TTx was not inferior to that of unifocal PTC. Immediate completion thyroidectomy is not necessary when microscopic foci are proven.

Role of postoperative chemoradiotherapy in head and neck cancer without positive margins or extracapsular extension: a propensity score-matching analysis

BackgroundThe aim of this work was to determine whether patients with intermediate-risk head and neck squamous cell carcinoma (HNSCC) can benefit from postoperative chemoradiotherapy (POCRT).MethodsPatients without extracapsular extension (ECE) or positive margins (PMs) who received POCRT or postoperative radiotherapy (PORT) at our center were retrospectively (December 2009 to October 2018) included for analysis, in particular, using a propensity score-matching method.ResultsAfter matching, 264 patients were enrolled, including 142 (41.2%) patients with pT3-4, 136 (38.3%) patients with pN2-3, 68 (21.1%) patients with perineural invasion, and 45 (12.8%) patients with lymphatic/vascular space invasion. With a median follow-up of 52 months, 3-year overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and disease-free survival (DFS) rates were 72.4%, 79.3%, 83.5% and 62.5%, respectively. pN2-3 was an independent risk factor for OS (p < 0.001), DFS (p < 0.001), LRFS (p < 0.001) and DMFS (p = 0.002), while pT3-4 was a poor prognostic factor for DMFS (p = 0.005). Overall, patients receiving POCRT had no significant differences from those receiving PORT in OS (p = 0.062), DFS (p = 0.288), LRFS (p = 0.076) or DMFS (p = 0.692). But notably, patients with pN2-3 achieved better outcomes from POCRT than PORT in 3-year OS (p = 0.050, 63.9% vs. 47.9%) and LRFS (p = 0.019, 74.6% vs. 54.9%). And patients with pT3-4 also had higher 3-year LRFS (p = 0.014, 88.5% vs. 69.1%) if receiving POCRT.ConclusionsAmong all intermediate-risk pathological features, pN2-3 and pT3-4 were independent unfavorable prognostic factors for patients with HNSCC without PMs or ECE. POCRT can improve the survival outcomes of patients with pN2-3 or pT3-4.

Level II Oncoplastic Surgery as an Alternative Option to Mastectomy with Immediate Breast Reconstruction in the Neoadjuvant Setting: A Multidisciplinary Single Center Experience.

Simple SummaryIn patients with breast cancers larger than 2 cm undergoing neoadjuvant chemotherapy, there is a poor evaluation regarding the equivalence between oncoplastic surgery level II (OPSII) and mastectomy with immediate breast reconstruction (MIBR) regarding the aesthetic and oncological outcomes. The aim of our retrospective study was to assess whether OPSII is a safe alternative to MIBR. We confirmed the uniformity of the two techniques after neoadjuvant chemotherapy concerning loco-regional and systemic disease-free survival and overall survival in a population of 297 patients (87 undergoing OPSII, and 210 MIBR). In addition, we have highlighted how OPSII results in a lower loss of breast sensitivity after surgery and a better physical well-being of the chest. Therefore, in selected cases, OPSII should be preferred over MIBR, as it does not affect the oncological outcome, but improves physical well-being and allows the preservation of breast sensitivity in patients undergoing surgical treatment.Oncoplastic surgery level II techniques (OPSII) are used in patients with operable breast cancer. There is no evidence regarding their safety and efficacy after neoadjuvant chemotherapy (NAC). The aim of this study was to compare the oncological and aesthetic outcomes of this technique compared with those observed in mastectomy with immediate breast reconstruction (MIBR), in post-NAC patients undergoing surgery between January 2016 and March 2021. Local disease-free survival (L-DFS), regional disease-free survival (R-DFS), distant disease-free survival (D-DFS), and overall survival (OS) were compared; the aesthetic results and quality of life (QoL) were evaluated using BREAST-Q. A total of 297 patients were included, 87 of whom underwent OPSII and 210 of whom underwent MIBR. After a median follow-up of 39.5 months, local recurrence had occurred in 3 patients in the OPSII group (3.4%), and in 13 patients in the MIBR group (6.1%) (p = 0.408). The three-year L-DFS rates were 95.1% for OPSII and 96.2% for MIBR (p = 0.286). The three-year R-DFS rates were 100% and 96.4%, respectively (p = 0.559). The three-year D-DFS rate were 90.7% and 89.7% (p = 0.849). The three-year OS rates were 95.7% and 95% (p = 0.394). BREAST-Q highlighted significant advantages in physical well-being for OPSII. No difference was shown for satisfaction with breasts (p = 0.656) or psychosocial well-being (p = 0.444). OPSII is safe and effective after NAC. It allows oncological and aesthetic outcomes with a high QoL, and is a safe alternative for locally advanced tumors which are partial responders to NAC.

Abstract P3-18-16: Breast conserving surgery in BRCA-mutation carriers. A single Institution experience

Abstract BackgroundBRCA-mutation carriers have a lifetime risk of breast cancer (BC) that ranges from 36 to 70%. For patients (pts) without mutation, breast conserving surgery (BCS) (followed by radiation therapy) is the treatment of choice since it offers similar survival to that of unilateral mastectomy. However, the optimal local management in BRCA-mutation carriers remains a matter of debate and the role of bilateral salpingo-oophorectomy (BSO) in reducing BC risk might be influenced by age and medical BC treatments (such as GnRH analogues). Patients and methodsWe retrieved clinical pathologic characteristics of 124 BRCA-mutated BC pts, consecutively tested at our Institution from 2008 to 2018. Primary end-point was recurrence-free survival (RFS) evaluation in terms of disease-free survival (DFS), distant DFS (DDFS) and overall survival (OS). Secondary end-point was identification of independent predictive factors for BCS. Clinical pathologic characteristics were evaluated and compared using univariate and multivariate analysis. Kaplan-Mayer curves were used to describe DFS, DDFS and OS. ResultsMedian age at BC surgery was 41 years (range 24-74), most of the pts (79%) were pre-menopausal and presented with ductal invasive carcinoma (91.9%). As per biological subtype, 63 (50.8%) pts had luminal-like BC, 52 (41.9%) triple negative (TN) BC and 9 (7.3%) HER2 enriched-like BC. More than half pts (62.9%) presented with G3 tumors and median Ki-67 was 40% (range 5-95). 17 (13.7%) and 80 (64.5%) pts underwent neo-adjuvant and adjuvant chemotherapy, respectively; 64 (51.6%) pts received adjuvant endocrine therapy, 39 (31.5%) with the addition of GnRH analogue. When comparing BCS to mastectomy, regardless of BSO, we could not observe any statistically significant difference in all the RFS end-points. 10-year DFS rate was 56.4% and 79.5%, respectively (p=0.187); 10-year DDFS rate was 83.7% and 82.3%, respectively (p=0.689); 10-year OS rate was 87.7% and 85.1%, respectively (p=0.947). At a multivariate analysis, age ≤41 years (p=0.008; OR 0.309; 95% CI 0.190-0.513) and primary tumor dimension ≤21 mm (p=0.008; OR 0.320; 95% CI 0.114-0.426), were the only predictors of breast surgery type (BCS compared to any other surgical treatment). ConclusionsOur data suggest that young pre-menopausal BRCA-mutated pts with small tumors may not need up-front mastectomy and BSO might be postponed, when ovarian cancer risk epidemiologically rises and potential reproductive desire is fulfilled. Citation Format: Agnese Losurdo, Damiano Gentile, Monica Zuradelli, Andrea Sagona, Erika Barbieri, Monica Barile, Paolo Bianchi, Rosalba Torrisi, Wolfgang Gatzemeier, Marta Scorsetti, Corrado Tinterri, Armando Santoro. Breast conserving surgery in BRCA-mutation carriers. A single Institution experience [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-16.

Prognostic Relevance of Change in Body Mass Index in Patients With Nasopharyngeal Carcinoma Undergoing Volumetric Modulated Arc Therapy: A Retrospective Study.

ObjectiveTo assess the effect of pretreatment body mass index (BMI) and the extent of change in BMI (ΔBMI) during the treatment course on the treatment outcomes in patients with nasopharyngeal carcinoma (NPC) receiving volumetric modulated arc therapy (VMAT).MethodsData pertaining to 498 consecutive NPC patients with stage I–IVA disease who received VMAT between January 2010 and November 2011 at a single center were retrospectively analyzed. Univariate Kaplan-Meier and multivariate Cox regression analyses were used to evaluate the prognostic significance of pretreatment BMI and ΔBMI. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off point of ΔBMI.ResultsThe 5-year loco-regional failure-free (L-FFR), distant failure-free survival (D-FFR), disease-free survival (DFS), and overall survival (OS) rates were 90.6%, 83.7%, 71.5% and 79.3%, respectively. The 5-year L-FFR, D-FFR, DFS, OS rates for NPC patients with ΔBMI ≤1 kg/m2 vs ΔBMI >1 kg/m2 were 92.3% vs 89.3% (P = .137), 90.9% vs 78.5% (P < .001), 80.4% vs 65.1% (P < .001), and 88.0% vs 73.0% (P < .001), respectively. ΔBMI >1 kg/m2 was an independent predictor of D-FFR (P = .002), DFS (P = .002), and OS (P = .001).ConclusionsΔBMI during treatment course may have a significant impact on the prognosis of NPC patients receiving VMAT.

Efficacy of concurrent chemoradiotherapy in subgroups of stage III nasopharyngeal carcinoma: an analysis based on 10-year follow-up

PurposeTo evaluate the efficacy of concurrent chemoradiotherapy (CCRT) in subgroups of stage III nasopharyngeal carcinoma (NPC) in the context of intensity-modulated radiotherapy (IMRT).MethodsA total of 272 patients with stage III NPC who underwent IMRT with or without concurrent chemotherapy were retrospectively reviewed. Clinicopathological features were evaluated by a Cox regression model to identify independent prognostic factors. Survival outcomes were assessed using the Kaplan–Meier method and log-rank test.ResultsThe median follow-up time was 108 months. The 10-year locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 87.8%, 80.7%, 68.8%, and 74.9%, respectively. Multivariate analysis showed that the N classification was significantly associated with DMFS (hazard ratio [HR] 3.616, 95% confidence interval [CI] 1.387–9.428, P = 0.009), DFS (HR 2.417, 95% CI 1.291–4.423, P = 0.006), and OS (HR 3.024, 95% CI 1.385–6.602, P = 0.005). In patients with T1-3N2 disease, CCRT was associated with improved 10-year LRFS (89.6% vs. 65.4%, P = 0.005), DFS (71.9% vs. 39.4% P = 0.001) and OS (80.0% vs. 50.5%, P = 0.004) compared with IMRT alone. However, in patients with T3N0-1 disease, no significant survival differences were observed between patients treated with IMRT alone and CCRT (P > 0.05).ConclusionsCCRT is an effective therapy in stage III NPC, especially for patients with N2 disease, but IMRT alone may be adequate for N0-1 disease. Individualized treatment strategies are essential for patients with varying disease risks.

Clinical Profile and Treatment Outcomes in Patients Treated with Intensity-Modulated Radiotherapy (IMRT) for Carcinoma Nasopharynx: A Retrospective Analysis.

Objective To retrospectively evaluate the clinical outcome of carcinoma nasopharynx patients treated with the IMRT technique. Methods Eighty-one nasopharyngeal carcinoma patients who were treated with IMRT with or without chemotherapy between the period January 2011 and December 2014 at a comprehensive tertiary cancer center, Kerala, India, were included in the study. The mean age was 43 years (range 13–77 years), and majority of the patients were males (67.9%). The stagewise distribution of disease at presentation was 2 (2.5%) in stage I, 19 in stage II (23.5%), 31 (38.3%) in stage III, and 29 (35.8%) in stage IV. All patients were treated using simultaneous integrated boost (SIB) schedule using IMRT with 6 MV photon to a dose of 66 Gy in 30 fractions, 2.2 Gy per fraction prescribed to high-risk PTV; 60 Gy in 30 fractions, 2 Gy per fraction to intermediate risk PTV; and 54 Gy in 30 fractions, 1.8 Gy per fraction to low-risk PTV. Concurrent chemotherapy with cisplatin was offered to patients with stage II and above disease. Neoadjuvant chemotherapy with cisplatin and 5FU was given to patients with initially advanced disease (T3, T4, N2, and N3). Survival estimates were generated using the Kaplan–Meier method. The univariate analysis was performed using log-rank tests. Results The 5-year locoregional control (LRC), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 87.5%, 87%, 61.6%, and 62.5%, respectively. The 5-year OS was 100% for stage I (n = 2), 67% for stage II (n = 19), 70.4% for stage III (n = 31), and 68.1% for stage IV (n = 29). The DFS at 5 years was 100% for stage I, 61.1% for stage II, 56.2% for stage III, and 84.8% for stage IV disease. The univariate analysis showed that age, nodal stage, and use of induction chemotherapy showed an improved trend towards OS, though the results were not statistically significant. The predominant pattern of failure in the present study was distant metastasis. Most patients who developed distant metastasis in our study had either an advanced T stage or N3 disease at presentation. Conclusion The present study shows our initial experience with IMRT for nasopharyngeal carcinoma. The compliance to RT was good in this study. The 5-year LRC and OS rate of nasopharyngeal carcinoma patients treated with IMRT were 87.5% and 62.5%. Distant metastasis was the main pattern of failure.

Sublobar resection with intraoperative brachytherapy versus sublobar resection alone for early-stage non-small-cell lung cancer: a meta-analysis.

The purpose of this study was to compare the clinical outcomes for sublobar resection (SR) or SR plus intraoperative brachytherapy (SRB) for clinical stage I non-small-cell lung cancer. A systematic search was performed in the EMBASE, PubMed and Cochrane Library databases to identify related studies comparing SR to SRB. Data were collected on local recurrence (LR) as a primary outcome and regional or distant recurrence, overall survival and disease-free survival (DFS) as secondary outcomes. Meta-analysis was carried out using Stata 12.0. A total of 476 patients received SRB, and 617 received SR across 5 studies. Meta-analysis of LR, regional or distant recurrence, overall survival and disease-free survival rates showed no significant difference between SRB and SR groups. However, when biologically effective dose (BED) was >100 Gy, LR rate was lower in the SRB group than in the SR group (Relative risk [RR] = 0.143, 95% confidence interval [CI]: 0.051-0.397) (p < 0.001). When BED was <100 Gy, no significant difference was found in LR rate between SRB and SR groups (SRB versus SR: RR = 1.132, 95%CI: 0.704-1.821) (p = 0.608). Intraoperative brachytherapy was not associated with reduced risk of regional or distant metastasis or improved outcomes for patients with clinical stage I non-small-cell lung cancer; however, it might reduce the LR rate when BED was >100 Gy.

Long-term recurrence rate and survival in different aged patients with breast cancer undergoing breast conserving therapy

Objective: To examine the difference of long-term recurrence rate and survivals between the young patients and the old patients undergoing breast conserving therapy (BCT). Methods: Women with primary invasive breast cancer receiving BCT between December 1999 and December 2014 were selected retrospectively from the database of Breast Cancer Center, Peking University Cancer Hospital & Institute. The median age of all patients was 47 years (range: 21 to 91 years). The cases were categorized according to age at diagnosis into two subgroups: the ≤40 years group and the>40 years group. A total of 2 778 patients were included: 677 patients in the ≤40 years group and 2 101 patients in the >40 years group. Clinicopathological characteristics between two groups were compared. The recurrence rate and survival were calculated using the Kaplan-Meier method. The differences of outcomes were compared in different aged groups using the Log-rank test. Factors affecting local recurrence, distant disease-free survival (DDFS), disease-free survival (DFS), and breast cancer-specific survival (BCSS) were assessed by multivariable Cox proportional hazard models. Results: Proportions of T1 (301/677 vs. 1 160/2 101, χ²=37.660, P<0.01), involved lymph node (314/677 vs. 713/2 101, χ²=34.966, P<0.01) hormone receptor-negative (490/677 vs. 1 581/2 101, χ²=6.981, P=0.030) and neoadjuvant chemotherapy (413/677 vs. 1 010/2 101, χ²=34.272,P<0.01)in the ≤40 years group were higher than that in the>40 years group. Median follow-up duration was 102 months. No significant difference in 10-year local recurrence was found between the two groups (2.5% vs. 1.6%, P=0.147). Ten-year DDFS rate in the ≤40 years group and in the>40 years group was 90.6% and 95.3%, respectively (P<0.01). Ten-year DFS rate in the ≤40 years group and in the>40 years group was 86.5% and 91.1%, respectively (P=0.001). Ten-year BCSS rate in the ≤40 years group and in the >40 years group was 91.0% and 93.7%, respectively (P=0.105). Age was not the prognosis factor of local recurrence. Lymph node status (positive vs. negative: HR=2.73, 95%CI: 1.94 to 3.84, P<0.01), age (≤40 years vs.>40 years: HR=1.73, 95%CI: 1.24 to 2.42, P=0.001) and T stage (>2 cm vs. ≤2 cm: HR=1.61, 95%CI: 1.14 to 2.28, P=0.001) were the prognosis factors of DDFS, and also for DFS. Hormone receptor status (positive vs. negative: HR=0.54, 95%CI: 0.39 to 0.74, P<0.01), lymph node status (positive vs. negative: HR=2.94, 95%CI: 2.12 to 4.07, P<0.01) and T stage (>2 cm vs. ≤2 cm: HR=1.45, 95%CI: 1.05 to 2.01, P=0.025) were the prognosis factors of BCSS. Conclusions: The risk of local recurrence was similar between ≤40 years patient and >40 years patients receiving breast conserving therapy. Worse survivals in the ≤40 years group were found comparing to those in the >40 years group.

Postoperative Adjuvant Anastrozole for 10 Rather than 5 Years in Patients with Oestrogen Receptor-Positive Breast Cancer: AERAS, a Randomised Multicentre Open-Label Phase III Trial

Background: Treatment with an aromatase inhibitor for 5 years is the standard treatment for postmenopausal hormone receptor-positive breast cancer. We investigated the effects of extending this treatment to 10 years on the risk of breast cancer recurrence. Methods: This prospective, randomised, multicentre open-label phase III study assessed the effect of extending anastrozole treatment for an additional 5 years in postmenopausal patients with stage I–IIIA hormone receptor-positive breast cancer who were disease-free after treatment with either 5 years of anastrozole alone or 2–3 years of tamoxifen followed by 2–3 years of anastrozole. Patients were allocated randomly (1:1) to continue anastrozole (1 mg/day orally) for an additional 5 years or stop anastrozole, using the central computer at the Comprehensive Support Project for Oncology Research Data Centre. Randomisation was stratified by type of postoperative endocrine therapy, nodal status, prior adjuvant chemotherapy, and facility. The primary endpoint was disease-free survival, including breast cancer recurrence, second primary cancers, and death from any cause. This study is registered with UMIN clinical trials registry, number UMI00818. Findings: We enrolled 1697 patients from 117 facilities between November 2007 and November 2012. Patients were assigned randomly to the continue group (n=849) or the stop group (n=848). Follow-up information was available for 1593 patients (n=787 in the continue group, n=806 in the stop group) as the full analysis set. After a median follow-up of 5·1 years, there were 172 events involving disease recurrence or the occurrence of contralateral breast cancer (75 in the continue group and 97 in the stop group) and 40 deaths (21 in the continue group and 19 in the stop group). The 5-year disease-free survival rates were 91% (95% confidence interval [CI] 89–93) in the continue group and 86% (95% CI 83–88) in the stop group (hazard ratio [HR] for disease-free survival 0·61, 95% CI 0·46–0·82; p<0·0010, two-sided log-rank test). The 5-year overall survival rates were 98% in the continue group and 98% in the stop group (HR 1·13, p=0·7042). The 5-year distant disease-free survival rates were 95% in the continue group and 93% in the stop group (HR 0·68, p=0·0553). Sixty-seven second primary cancers occurred, including 24 in the continue group and 43 in the stop group. Menopausal or bone-related all-grade adverse events were more frequent among patients in the continue group than in the stop group, including higher incidences of hot flashes (111 [14%] vs 81 [10%]), stiff joints (162 [21%] vs 98 [12%]), arthralgia (294 [37%] vs 236 [29%]), and new-onset osteoporosis (370 [47%] vs 355 [44%]). Interpretation: Continuing adjuvant anastrozole for an additional 5 years after 5 years’ initial treatment with anastrozole or tamoxifen is safe and beneficial in postmenopausal patients with hormone receptor-positive breast cancer. Trial Registration: This study is registered with UMIN clinical trials registry, number UMI00818. Funding: The Comprehensive Support Project for Oncology Research of the Public Health Research Foundation Declaration of Interest: None to declare. Ethical Approval: Ethical approval was provided by local ethics committees in each hospital.

Response and Prognosis of Docetaxel and Cyclophosphamide as Neoadjuvant Chemotherapy in ER+ HER2− Breast Cancer: A Prospective Phase II Study

BackgroundAlthough a docetaxel and cyclophosphomide (TC) regimen without anthracycline as adjuvant therapy became one of the standard regimens especially for ER-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) primary breast cancer, the efficacy of TC as neoadjuvant chemotherapy (NAC) is not known. We conducted the prospective trial to assess the efficacy of a TC regimen in the neoadjuvant setting for stage II to III ER+/HER2− primary breast cancer. Patients and MethodsA TC regimen that included 75 mg/m2 of docetaxel and 600 mg/m2 of cyclophosphamide for 4 cycles every 3 weeks was administered as NAC. Primary endpoints are the rate of clinical response (clinical partial response and clinical complete response) and pathologic complete response; secondary endpoints are the disease-free survival and overall survival rates. ResultsThirty (71.4%) of 42 tumors had clinical response. No patient achieved pathologic complete response. At the median follow-up period of 105.2 months (range, 12.1-119.7 months), the disease-free survival rate was 81.6%, and the distant disease-free survival rate was 86.8%. In terms of survival, only 1 patient died during the study period. The overall survival rate was 97.4% during the study period. Patients who developed distant recurrence had a trend to have progesterone receptor-negative or weakly positive compared with those who did not develop any recurrence (85.7% vs. 45.2%; P = .05). ConclusionsOur prospective study showed that a TC regimen as NAC achieved a high clinical response rate in stage II to III ER+/HER2− breast cancer. A TC regimen without anthracycline as NAC might be one of the options for patients with ER+/HER2− breast cancer without high-risk factors including progesterone receptor negativity.

Predictive factors for omitting lymphadenectomy in patients with node-positive breast cancer treated with neo-adjuvant systemic therapy.

A pathologic complete response (pCR) in the axilla occurs in 30%-40% of patients with initially node-positive breast cancer after neo-adjuvant chemotherapy (NACT). Debate persists about whether to perform systematic axillary lymphadenectomy (ALND) in patients with initial node-positive disease and clinical complete response after NACT. We aimed to identify predictive factors of axillary pCR (ypN0) after NACT. This retrospective study analyzed data for all patients with initial biopsy-proven node-positive disease who underwent ALND after NACT between June 2008 and December 2016 at our institution. Clinical and pathologic features, recurrence and specific mortality rates were compared between patients who achieved an axillary pCR and those who did not (ypN0 vs ypN+, respectively). A total of 331 patients were included, of whom 128 (38.7%) became ypN0 after NACT. Among patients with >2 suspicious axillary lymph nodes before treatment, 54 (38%) achieved ypN0 status. The independent predictors of ypN0 were Ki-67>30 (OR 1.98; 95% CI, 1.146-3.381), HER2 positivity (OR 2.6; 95% CI, 1.354-5.108), nonluminal molecular-like subtype (OR 4.15; 95% CI, 2.068-5.108), and clinical complete response, defined as negative clinical and ultrasonographic findings (OR 2.8; 95% CI, 1.110-7.081). After a mean follow-up of 61months, distant disease-free and overall survival rates were higher in patients with ypN0 disease (HR 4.14; 95% CI, 2.03-8.43) than ypN+ patients. Complete clinical response and the presence of nonluminal molecular-like subtypes independently predicted ypN0. Patients meeting these criteria might be suitable form omitting ALND and just performing targeted axillary procedures to patients meeting these criteria.

1070PD - Treatment outcomes and pattern of failure in primary gastric diffuse large B cell lymphoma with complete remission following R-CHOP chemotherapy

BackgroundThe optimal treatment for primary gastric diffuse large B cell lymphoma (DLBCL) is unclear. The treatment for primary gastric DLBCL is in accordance with the principle of treatment for general DLBCL. We aimed to evaluate the treatment outcomes and pattern of failure in primary gastric DLBCL. MethodsBetween April 2001 and November 2018, 120 patients with stage I–IV primary gastric DLBCL were retrospectively reviewed in this study. All patients had been in complete remission after receiving rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Ninety patients (75%) were treated with R-CHOP alone, and the other 30 patients (25%) underwent R-CHOP with local treatment for gastric lesions. Twelve patients (10%) underwent gastrectomy, and 18 patients (15%) received consolidation radiotherapy (RT). ResultsThe median follow-up time was 49 (range, 5 to 197) months. The 5-year locoregional failure-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 85.6%, 86.5%, 83.4%, and 90.3%, respectively. During the follow-up, 17 patients (14.2%) experienced disease recurrence. Only 3 patients developed distant metastasis without locoregional failure (LRF). All except two cases of LRF included gastric failure. There was no LRF in patients who received R-CHOP with local treatment. On multivariate analysis, poor performance status was an independent prognostic factor for LRFS, and multiple gastric lesions influenced LRFS, DMFS, DFS, and OS. ConclusionsThe main pattern of initial failure is LRF, especially in the stomach in patients with primary gastric DLBCL. Gastric local treatment such as consolidation RT can effectively prevent gastric failure. Therefore, gastric local treatment should be considered for patients at high risk of LRF, such as multiple gastric lesions. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.