Differences In Distant Metastasis-free Survival Research Articles

70-Gene signature-guided adjuvant systemic treatment adjustments in early-stage ER+ breast cancer patients: 7-year follow-up of a prospective multicenter cohort study.

A previous prospective multicenter study revealed the change of the oncologists' chemotherapy advice due to the 70-Gene signature (GS) test result in half of the estrogen receptor-positive (ER+) invasive early-stage breast cancer patients with disputable chemotherapy indication. This resulted in less patients receiving chemotherapy. This study aims to complement these results by the 7-year oncological outcomes according to the 70-GS test result and the oncologists' pre-test advice. Patients operated for early-stage ER+ breast cancer with disputable chemotherapy indication, had been prospectively included between 2013 and 2015. Oncologists were asked whether they intended to administer adjuvant chemotherapy before deployment of the 70-GS test. Information on adjuvant systemic treatment and oncological outcome was obtained through active follow-up by data managers of the Netherlands Cancer Registry. The primary endpoint of this study was distant metastasis-free survival (DMFS) according to the genomic risk. Exploratory analyses were done to evaluate DMFS in relation to the oncologists' pre-test advice. After a median follow-up of 7 years, distant metastases were diagnosed in 23 of the 606 patients (3.8%) and 36 (5.9%) patients had died. The DMFS rate for the 357 70-GS genomic low-risk patients was 94.2% (95% CI 91.2-96.2) and 89.1% for the 249 genomic high-risk patients (95% CI 84.3-92.4). Of the low-risk patients 3% had received chemotherapy compared to 80% of the high-risk patients. For the subgroups based on the pre-test oncologists' advice (no chemotherapy/chemotherapy/unsure) there were no clinically relevant differences in DMFS (89.8, 93.2 and 92.0%, respectively), while comparable proportions of patients had received chemotherapy. In patients with early-stage ER+ breast cancer with a disputable chemotherapy indication it is sensible to deploy the 70-GS to better select patients for adjuvant chemotherapy.

Prognostic Evaluation of HER2-positive Early Breast Cancers Using Clinico-pathological Criteria.

HER2-positive breast carcinomas (BCs) generally behave more aggressively and show higher cytological and histological grade than HER2-negative BCs. However, the clinical properties of HER2-positive early BCs have not been studied extensively. Hence, the therapeutic significance of neoadjuvant chemotherapy (NAC) for this BC remains debatable. We retrospectively examined the clinicopathological features of 94 HER2-positive early BCs who perioperatively received anti-HER2 drugs, without undergoing NAC prior to surgery. The patients' five year-disease free survival (DFS) and overall survival (OS) rates were 95.6% and 100%, respectively. Univariate analysis demonstrated significant differences in distant metastasis-free survival (DMFS) between clinical and pathological tumor stages (T stages). Pathological T1 stage and clinical T1 stage tumors showed significantly higher DMSF than pT2-3 and cT2-3 (p=0.0002 and 0.0294). Multivariate analysis disclosed no significant differences in DFS, OS, and DMFS with respect to preoperative clinical tumor stage, patient age, type of surgery, postoperative therapy, and pathological factors. Recurrences occurred in nine patients: four (4.3%) and five (5.3%) patients showed local and distant recurrences, respectively. One patient with cT2 BC died of disease. Interestingly, four of the five BCs with distant recurrence pathologically demonstrated lymph vessel invasion. The prognoses of patients with HER2-positive stage cT1/2N0M0 BC were highly favorable. The indications for NAC in small, localized, and node-negative HER2-positive BC should be carefully assessed based on the presence of a larger tumor size, postoperative pathological evaluation of tumor size, and lymph vessel invasion.

Abstract PO5-01-12: Factors Influencing Late Recurrence in Breast Cancer: A Comprehensive Analysis of the Impact of Hormone Therapy Regimens

Abstract Late recurrence of breast cancer remains a significant challenge in patient management. Despite the established efficacy of hormone therapy, factors influencing late recurrence and the impact of different hormone therapy regimens on this outcome are not yet fully understood. This study aims to investigate the key determinants contributing to late recurrence within the context of different hormone therapy regimens. This study is a retrospective analysis of medical records from two institutions between 1988 and 2018, specifically examining patients who had HR-receptor positive breast cancer who underwent surgery and completed a 5-year course of standard hormone therapy. Primary endpoint is to identify the demographic, clinical and pathologic factors as associated with late recurrence. Out of 1929 eligible patients, 49.6% (956) received Tamoxifen (TMX), 37.6% (726) received Aromatase inhibitors (AI), and 12.8% (247) switched between regimens (TMX to AI or AI to TMX). Median follow-up was 12.1 years (3.75 - 21.41 years). During this period, all-type recurrence (ATR) occurred in 9.3% of all patients, with higher rates in the TMX recipients (12.2%). Locoregional and contralateral recurrence were identified in 10.6% of TMX recipients, 6.5% of patients who switched regimens, and 5% of AI recipients. In all patients, 5.4% were diagnosed with distant metastasis, with slightly higher rates in the TMX recipients (6.4%). Multiple sites in the bone, lung, liver and brain (34.3%) was the most prevalent location of distant metastasis (DM), followed by soft tissue (20%), liver (16.2%), bone (10.5%), lung (8.6%), and other locations. Significant differences in recurrence-free survival (RFS) were observed between hormone therapy groups (p=0.004, log-rank test). Mean overall RFS was 20.4 years (95% C.I. 20.1-20.9 years). TMX recipients had a mean RFS of 19.8 years, AI recipients had a mean RFS of 18.3 years and those who switched regimens had a mean RFS of 21.9 years. Further analysis showed premenopausal patients who switched regimens had higher RFS (p=0.014). No significant difference in RFS was seen between premenopausal patients receiving AI or Tamoxifen, or amongst post-menopausal patients with different hormone therapy regimens. No significant difference in distant metastasis-free survival (DMFS) was observed between hormone therapy groups (p=0.442). Mean overall DMFS was 21.5 years (95% C.I. 21.2 - 21.8 years), with TMX patients 21.1 years, AI patients at 18.6 years, and those who switched regimens at 21.4 years. Sub-analyses of DMFS in pre and postmenopausal patients with different hormone therapy regimens showed no significant differences. Multivariate analysis showed tumor size ≤ 2cm (p= 0.0001) and negative axillary node involvement (p= 0.0001) significantly decreased odds of developing late all-type recurrence (ATR) in TMX recipients. In patients who switched regimens, Her2 positivity (p=0.04) significantly decreased the odds of late ATR. In AI recipients, not undergoing axillary operation (p = 0.008) significantly increased the odds of late ATR. For TMX recipients, negative axillary node involvement (p=0.004), tumor size ≤ 2cm (p=0.03), and undergoing mastectomy (p=0.02) significantly decreased odds of distant metastasis (DM). Among patients who switched regimens, adjuvant anti-Her2 therapy (p=0.02) significantly decreased odds of DM. For AI recipients, high PR score (p=0.02) and undergoing sentinel lymph node biopsy significantly decreased odds of DM, while age < 50 years significantly increased odds of developing DM. These findings emphasize the significance of the relationship between hormone therapy regimens and factors affecting late recurrence, thereby providing valuable insights for clinical decision-making. Risk stratification based on identified factors can help in identifying patients at higher risk of late recurrence allowing for more intensive surveillance and potentially early intervention. Univariate (Chi-square, Logistic Regression) and Multivariate Analysis (Logistic Regression) for Clinicopathologic factors associated with all-type recurrence and distant metastasis after surgery and completion of 5-years endocrine therapy Table. a. LN lymph node b. SLNB, Sentinel lymph node biopsy c. ALND, Axillary lymph node dissection d. Cutoff values of Ki67 14% in KUAH and 10%in SNUH e. ER and PR cutoff value is 10% f. UV, Univariate analysis, MV multivariate analysis, O.R. Odds Ratio, C.I. Confidence Interval Citation Format: Mary Rose Mendoza, Eun-Shin Lee. Factors Influencing Late Recurrence in Breast Cancer: A Comprehensive Analysis of the Impact of Hormone Therapy Regimens [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 PO5-01-12.

Abstract PO5-09-01: Relative low body mass index (BMI) and fat quantity predicts prognosis better than absolute BMI in hormone receptor-positive, HER2-negative breast cancer

Abstract Purpose: Most existing research about obesity and prognosis in breast cancer patients primarily compares obese and non-obese individuals according to standard body mass index (BMI) categories. With a notably high percentage of Asian patients presenting with young age onset and normal weight, the prevalence of overweight and obesity based on absolute BMI values is lower in Asia (according to WHO guideline, BMI under 18.5 means underweight, and BMI over 25 means overweight). Understanding the impact of relatively low and high weight on prognosis can provide more insightful data than assessments based on absolute BMI thresholds. This study aimed to investigate the impact of relative low/high BMI on the prognosis of breast cancer and to explore the influence of body fat quantity (FQ), which is closely related to BMI. Methods: The study population consisted of 3,663 patients who received surgery for primary breast cancer at Seoul National University Hospital from 2006 to 2015. Pre-treatment BMI was divided into quartiles, defining low-BMI (Q1) as ≤ 21.33, high-BMI (Q4) as > 25.53, and mid-BMI as values between the two. Fat quantity (FQ) was derived from chest CT using the deep learning-based FDA-approved DeepCatch software. It measures the fat volume at the L1 level then divides this value by the square of the patient's height. It was then also divided into quartiles, establishing the definitions of low-, mid-, and high-FQ. The associations of BMI and FQ with distant metastasis-free survival (DMFS) and overall survival (OS) were examined. Results: The high-BMI group demonstrated older median age and higher T and N stages (p< 0.001). The high- and low-BMI groups also showed a higher prevalence of estrogen receptor positive cancer compared to the mid-BMI group. A strong correlation (Pearson correlation coefficient 0.83) was observed between BMI and FQ. In HR-positive, HER2-negative breast cancer, high-BMI patients had a 1.55 times higher risk of distant metastasis (95% CI: 1.15-2.11, p = 0.005), and a 1.78 times higher risk of mortality (95% CI: 1.22-2.58, p = 0.003) compared to mid-BMI patients, while low-BMI patients demonstrated better outcomes regarding DMFS (HR 0.67, p=0.035) and OS (HR 0.59, p=0.04). Comparison of FQ with prognosis revealed that the low-FQ patients exhibited better DMFS (HR 0.59, p=0.005) and OS (HR = 0.44, p=0.002) compared to mid-FQ patients in HR-positive, HER2-negative breast cancer. However, when adjusted for T and N stages, low-BMI patients in the HR-positive, HER2-negative group showed no difference in prognosis from mid-BMI patients but better prognosis compared to high-BMI patients. In contrast, when defined using absolute BMI, underweight patients did not show a difference in DMFS (HR 0.72 vs. normal BMI, p = 0.515) and OS (HR 0.91 vs. normal BMI, p = 0.87) compared to those with normal weight and overweight. The low-FQ group had the best prognosis regarding DMFS (HR 0.66 vs. mid-FQ, p=0.032) and OS (HR 0.50 vs. mid-FQ, p=0.008). Conclusions: Low-BMI is a favorable prognostic factor compared to high-BMI for DMFS and OS in HR-positive, HER2-negative breast cancer. The relative BMI defined according to BMI quartiles was a better prognostic factor than to absolute BMI standards. Investigations with FQ showed similar tendencies, suggesting that low BMI's favorable prognostic influence may be associated with fat. Future investigations should aim to validate these results and delve deeper into the underlying mechanisms. Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Soon Ho Yoon work as chief medical officer in MEDICALIP. This author did not involve data/statistical analysis. Other authors have no competing interest to declare. Citation Format: Eunhye Kang, Ji-Jung Jung, Ik Beom Shin, Hawjeong Lee, Jin Young Byeon, Changjin Lim, Hong-Kyu Kim, Hyeong-Gon Moon, Wonshik Han, Jong-Ho Cheun, Soon Ho Yoon, Han-Byoel Lee. Relative low body mass index (BMI) and fat quantity predicts prognosis better than absolute BMI in hormone receptor-positive, HER2-negative breast cancer [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 PO5-09-01.

Optimal cut-off value for identifying objective response in patients with nasopharyngeal carcinoma after induction chemotherapy.

We aimed to establish the most suitable threshold for objective response (OR) in the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in patients with nasopharyngeal carcinoma (NPC). According to RECIST 1.1, we retrospectively evaluated MR images of NPC lesions in patients before and after induction chemotherapy (IC). Restricted cubic spline and maximally selected rank statistics were used to determine the cut-off value. Survival rates and differences between groups were compared with Kaplan-Meier curves and log-rank tests. Of 1126 patients, 365 cases who received IC treatment were suitable for RECIST 1.1 evaluation. The 20% cut-off value maximized between-group differences according to maximally selected rank statistics. No difference in distant metastasis-free survival between OR and non-response groups was shown using the primary threshold of OR (30%), while it differed when 20% was employed. With an optimal cut-off value of 20%, RECIST may assist clinicians to accurately evaluate disease response in NPC patients.

MammaPrint Index as a predictive biomarker for neoadjuvant chemotherapy response and outcome in patients with HR+HER2- breast cancer in NBRST.

521 Background: Hormone receptor positive (HR+), HER2- early stage breast cancer (ESBC) is a heterogeneous disease that has shown lower response to neoadjuvant chemotherapy (NCT) compared with other clinicopathologic subtypes. Genomic profiling may help inform neoadjuvant treatment decisions for ESBC by predicting likelihood of pathological complete response (pCR) or chemosensitivity. The 70-gene MammaPrint (MP) test classifies ESBC patients as having a Low or High Risk of distant metastasis. In the ISPY2 trial, further stratification of MP High Risk into High 1 (H1) or High 2 (H2) improved prediction of chemosensitivity, with significantly higher pCR rates in H2 vs. H1 tumors, particularly in response to immune therapy. Here we evaluate the utility of H1/H2 risk as a biomarker for chemosensitivity and 5 year distant-metastasis free survival (DMFS) in NCT treated patients from the Neoadjuvant Breast Registry Symphony Trial (NBRST). Methods: NBRST (NCT01479101) is an observational prospective study that included 1069 patients with ESBC who received neoadjuvant therapy. Patients with HR+HER2-, MP High Risk tumors who received NCT were included in this analysis (n = 327). Patients were further stratified into H1 (score ≤ 0, > -0.57) or H2 (score ≤ -0.57) groups. Differences in pCR between MP High Risk subcategories were assessed by two-sided proportional z-test. Differences in DMFS was evaluated by Kaplan Meier analysis and log-rank test. Results: MP classified 198 (61%) patients with H1 tumors and 129 (39%) patients with H2 tumors. Age, tumor stage, and lymph node status were comparable between both groups. However, there was a higher proportion of Grade 3 tumors in the H2 group. A significantly higher percentage of pCR was achieved in H2 tumors (30/129; 23%) vs. H1 tumors (12/198; 6.1%) (p < 0.001). Median follow-up was 5.3 years. The 5-year DMFS (% [95% CI]) was significantly worse for patients with H2 tumors (64.8 [55.9 – 75.1]), with most events occurring early ( < 3 years), compared with H1 tumors (77.1 [70.4 – 84.3]; p = 0.012). Patients with H1 tumors that achieved pCR had improved 5-year DMFS (81.8 [61.9 – 100]) compared to H1 tumors that did not achieve pCR (76.8 (69.9 – 84.4; p = 0.009). Patients with H2 tumors that had a pCR demonstrated significantly better 5-year DMFS (80.7 [65.3 – 99.8]) than patients with residual disease (60.2 [50.1 – 72.4]; p = 0.009). Conclusions: These data suggest MammaPrint predicts pCR in HR+HER2- BC patients, with H2 risk tumors exhibiting higher chemosensitivity than H1 tumors. Patients with either H1 or H2 tumors that achieved pCR had similar outcomes, which were significantly improved compared to those with residual disease. Notably, the worst outcomes were observed among patients with H2 risk and residual disease; it should be investigated whether addition of immune therapy to standard NCT would enhance the pCR rates in this patient population. Clinical trial information: NCT01479101 .

Role of Adjuvant Regional Nodal Irradiation in Resected Melanoma: A Secondary Analysis of SWOG S1404

<h3>Purpose/Objective(s)</h3> Results from TROG 02.01 demonstrated that adjuvant radiotherapy (RT) in high-risk melanoma patients is associated with improved locoregional control (LRC). The aim of our study is to evaluate the role of adjuvant RT in standard risk (SR), high risk (HR) and ultra-high risk (UHR) melanoma patients in the immunotherapy era. S1404 randomized resected stage III and stage IV melanoma patients to standard of care adjuvant immunotherapy or pembrolizumab after surgery. <h3>Materials/Methods</h3> We retrospectively analyzed the data for 1239 patients enrolled in S1404. We stratified the patients according to SR (no high-risk features), HR (defined according to TROG 02.01 trial) and UHR (extracapsular extension with 5 or more positive nodes or 4 cm or greater nodal size). Recurrence free survival (RFS) and time to regional recurrence (TtRR) were primary outcomes; distant metastasis free survival (DMFS) was a secondary outcome. RFS was estimated using the Kaplan-Meier method and associations with the outcome were evaluated using Cox regression models. TtRR and DMFS were estimated with cumulative incidence curves and associations with the outcome were evaluated using cause-specific regression models. <h3>Results</h3> Of 1239 patients analyzed, 136 patients (11%) completed RT. The most common RT regimen used was 30 Gy/5 fractions (37%) followed by 48 Gy/20 fractions (31%). Fifty three percent of patients were HR per TROG02.01. More HR patients received RT compared to SR (16 % versus 6%; p-value <= 0.001). Among the patients who received RT 76/136 (56%) were advanced stage (Stage IIIC/ resected Stage IV) compared with those who did not 390/1103 (35%); p value <= 0.001. Similarly macroscopic lymph node involvement was significantly higher in RT group, 89/136 (65%) versus 457/1103 (41%); p value <=0.001. TtRR was significantly longer for patients who completed RT (all comers: 9% RR @ 4 year no RT vs 1% @ 4 year with RT; p value = 0.015). For high-risk patients, TtRR was longer for patients who received RT regardless of PD1 status (12% RR @ 4 year no RT vs 2% @ 4 year with RT; p value = 0.009). No significant difference in value of RT was seen based on anatomic nodal site, study arm or BRAF mutation status. Among patients treated with pembrolizumab, a trend toward RFS benefit was seen in patients treated with RT (HR = 1.54, 95% confidence interval 0.94-2.53; p=0.085). There was no significant difference in DMFS between those who completed RT versus not. <h3>Conclusion</h3> Our study validated the results of previous studies and suggests consideration of adjuvant RT in high-risk patients regardless of planned adjuvant immunotherapy for improved LRC. We recommend the use of adjuvant RT in patients with macroscopic nodal involvement with extracapsular extension or with heavy nodal burden even in the immunotherapy era.

Influence of Adjuvant Radiotherapy Timing on Survival Outcomes in High-Risk Patients Receiving Neoadjuvant Treatments.

PurposeTo determine the relationship between time to radiotherapy (TTR) and survival outcomes in breast cancer (BC) patients treated with neoadjuvant treatments (NATs).MethodsContinuous non-metastatic BC patients receiving NAT and adjuvant radiotherapy (RT) from 2009 to 2016 were retrospectively reviewed. A multivariable Cox model with restricted cubic splines (RCSs) was used to determine the panoramic relationship between TTR and survival outcomes. Multivariable analysis was used to control for confounding factors between the groups of TTR.ResultsA total of 315 patients were included. The RCS modeling demonstrated a non-linear relationship between TTR and survival outcomes. The lowest risk for distant metastasis-free survival (DMFS) and recurrence-free survival (RFS) was observed at the TTR of 12 weeks, and the lowest risk of BC-specific survival (BCSS) at 10 weeks. TTR was accordingly transformed into categorical variables as ≤10, 11–20, and >20 weeks. Multivariable analysis revealed that the TTR of ≤10 weeks was an independent prognostic factor for worse DMFS (HR = 2.294, 95% CI 1.079–4.881) and RFS (HR = 2.126, 95% CI 1.038–4.356) compared with the TTR of 10–20 weeks, while the is no difference in DMFS, RFS, and BCSS between TTR >20 weeks and TTR of 10–20 weeks.ConclusionThere exists a non-linear relationship between TTR after surgery and survival outcomes in patients treated with NAT. Early initiation of RT following surgery does not seem to be associated with a better therapeutic outcome. A relatively flexible recommendation of TTR could be adopted in clinical practice.

Prophylactic lymphaticovenous bypass performed during complete lymphadenectomy is oncologically safe.

9557 Background: Lymphaticovenous anastomosis (LVA) is a physiologic surgery indicated for secondary lymphedema of the extremities, particularly for disease refractory to conservative management. Immediate lymphatic reconstruction (ILR) is prophylactic LVA concurrently performed with CLND. After the transected lymphatics are mapped through a dye injection, they are anastomosed to a nearby venous outflow tract. Though prophylactic LVA is increasingly being performed, its risk on cancer recurrence and distant metastasis is currently unknown. The purpose of this study was to compare the distant-metastasis free survival (DMFS) and relapse-free survival (RFS) times in melanoma patients who underwent prophylactic LVA during CLND versus those who underwent conventional CLND for grossly metastatic disease. Our study is the first prospective evaluation of the impact of prophylactic LVA on DMFS in patients undergoing CLND. Methods: This was a prospective study of patients with cutaneous melanoma who underwent CLND with concurrent LVA (LVA group) or CLND alone (comparison group) between 2012 and 2021. Patients were excluded if they had non-melanoma skin cancers, stage IV cancers before CLND, microscopic lymphatic disease only or follow-up time of less than 12 months who did not die from melanoma-related causes. The comparison group consisted of all consecutive patients that underwent CLND alone and met inclusion criteria. To reduce surgical technique variability, all cases were performed by a single, high-volume surgeon at a tertiary care center. Results: A total of 46 melanoma patients underwent prophylactic LVA during this time period. Twenty-three of these patients met all inclusion criteria and were included in the LVA group. Twenty-two consecutive patients that underwent CLND alone were included in the comparison group. All patients underwent either axillary or inguinal CLND. Average number of lymph nodes removed during CLND were 18.20 ± 9.61 and 17.04 ± 9.97 for the LVA and comparison groups, respectively (p = 0.69). Size of largest metastatic tumor in lymph nodes was 45.91 ± 35.03 mm and 44.54 ± 23.32 mm, respectively (p = 0.99). Average time to first recurrence diagnoses was 6.75 ± 3.54 months vs 8.28 ± 5.66 months. For distant metastases only, the average time to first recurrence diagnoses was 6.16 ± 3.79 months and 9.39 ± 6.19 months, respectively (p = 0.25). There was no significant difference in recurrence type between the two groups (p = 0.66). There were no differences in DMFS and RFS times between the LVA and comparison groups. Conclusions: Prophylactic LVA performed for grossly metastatic melanoma does not negatively impact DMFS nor RFS. Considering the extremely aggressive nature of melanoma, our finding is potentially applicable to other cancers that are amenable to CLND and LVA.

Prognostic value of quantitative cervical nodal necrosis burden on MRI in nasopharyngeal carcinoma and its role as a stratification marker for induction chemotherapy.

This study aimed to assess the prognostic value of quantitative cervical nodal necrosis (CNN) burden in N staging risk stratification in patients with nasopharyngeal carcinoma. Univariate and multivariate Cox regression models evaluated the association between lymph node variables based on MRI images and survival. Revisions for the N classification system were proposed and compared to the 8th edition AJCC staging system using Harrell's concordance index (C-index). The survival outcomes of induction chemotherapy plus concurrent chemoradiotherapy (CCRT) and CCRT alone in patients with multiple CNNs were compared. In 1319 patients enrolled, CNN was not an independent prognostic factor for the main survival outcomes, but multiple CNNs (three or more necrotic nodes) were independent prognostic factors for distant metastasis-free survival (DMFS) (adjusted hazard ratio [HR], 2.05; p = 0.020) and progression-free survival (PFS) (HR, 1.78; p = 0.004), surpassing other nodal variables. On upgrading patients with multiple CNNs to revised N3 disease, the proposed N staging widened the differences in DMFS and PFS between N2 and N3 disease. The overall survival of patients with multiple CNNs who received CCRT plus induction chemotherapy was improved compared to that of those who received CCRT alone (76.1% vs. 55.7%; adjusted p = 0.030). Upgrading patients with multiple CNNs to stage N3 may improve prognostication of the current AJCC staging system. Multiple CNNs might be a potential marker for stratifying patients who would benefit from induction chemotherapy. • Quantitatively assessed the prognostic value of CNN burden in patients with NPC. • Upgrading patients with multiple CNNs to stage N3 may improve prognostication. • Multiple CNNs may be used as a stratification marker for induction chemotherapy.

Short-term ADT and Dose-escalated IMRT in Patients With Intermediate-risk Prostate Cancer: Benefit or Caution?

In the era of dose-escalated prostate radiation therapy (RT), the use of androgen deprivation therapy (ADT) is undefined for intermediate-risk (IR) prostate cancer. There is growing concern of the risk of ADT to be detrimental to quality of life. This single-institution retrospective analysis aimed to evaluate outcomes of IR patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with or without concurrent/adjuvant short-term ADT. Data was collected from 260 consecutive patients treated with dose-escalated IMRT with daily image-guided RT for newly diagnosed IR prostate cancer. Biochemical recurrence-free survival (BCRFS), distant metastasis-free survival, prostate cancer-specific survival, and overall survival (OS) were calculated using Kaplan-Meier methodology. Median follow-up was 93 months. A total of 181 patients had unfavorable IR disease, and 36.2% (N=94) received ADT, with median ADT duration of 6 months. Seven-year BCRFS was 94.1% vs. 86.2% (P=0.067), for ADT and no ADT, respectively, and no difference in distant metastasis-free survival or prostate cancer-specific survival was observed. ADT was associated with significantly worse 7-year OS (80.0% vs. 91.3%, P=0.010). Analysis of the unfavorable IR cohort alone, showed similar results; 7-year BCRFS and 7-year OS in patients who received ADT versus no ADT were 93.7% vs. 85.9% (P=0.093), and 79.0% vs. 90.6% (P=0.019), respectively. In our 15-year experience treating IR prostate cancer with dose-escalated IMRT with daily image-guided RT, short-term concurrent ADT was associated with a statistically significant worse OS. Additional studies are needed to determine if ADT is beneficial or detrimental for patients with IR prostate cancer treated with dose-escalated radiation.

The role of surgery on locoregional treatment of patients with breast cancer newly diagnosed with ipsilateral supraclavicular lymph node metastasis.

Radiotherapy is a practical locoregional treatment approach for women with breast cancer who show ipsilateral supraclavicular lymph node metastasis (ISLNM) on diagnosis. However, there is controversy around the role of supraclavicular lymph node dissection. Therefore, we aimed to study the significance of supraclavicular surgery based on radiotherapy. We retrospectively reviewed the data of 142 patients with breast cancer who presented with isolated ISLNM and received radiotherapy between the years 2000 and 2016. We also defined the effect of surgery on locoregional treatment of these patients by analyzing the prognostic factors for recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS). We observed that, of the 142 patients, 104 who received radiotherapy underwent supraclavicular lymph node dissection. Also, among the study group, the progesterone receptor (PR) status (P = 0.044) and the number of axillary lymph nodes (ALNs) involved (P = 0.002) were significant independent predictors of RFS. Also, tumor size (P = 0.007), PR (P < 0.001), and number of ALNs (P < 0.001) were independent predictors of DMFS and were statistically significant. Also, PR was an independent prognostic factor of OS (P = 0.033), whereas the supraclavicular surgery was not an independent prognostic factor for RFS, DMFS, and OS. Furthermore, our study focused on 92 patients with negative estrogen receptors (ERs). The result showed that supraclavicular surgery was statistically significant for RFS (P = 0.023); no significant differences in DMFS and OS were found between patients who received supraclavicular surgery and those who did not. Radiotherapy may be the primary locoregional treatment approach for patients with breast cancer who present with newly diagnosed ISLNM. Additionally, supraclavicular surgery may be more appropriate for patients with negative ER who received radiotherapy.

Circulating tumor cells may serve as a supplement to RECIST in neoadjuvant chemotherapy of patients with locally advanced breast cancer.

Circulating tumor cells (CTCs) have been shown to be associated with the response to neoadjuvant chemotherapy (NCT) and the prognosis of locally advanced breast cancer (LABC) patients. Our study aimed to investigate whether the change of CTC status during NCT could serve as a supplement to the Response Evaluation Criteria in Solid Tumors (RECIST) in the treatment and evaluation of LABC patients. 6ml of blood samples were collected before NCT, after the first cycle of NCT and after the completion of NCT, respectively. According to the change of CTC number during NCT, the patients were divided into "CTC low-response (low-R)" group and "CTC high-response (high-R)" group. Survival data of each group of patients were obtained through long-term follow-up. A total of 35 patients diagnosed with LABC were enrolled. The median follow-up for distant metastasis was 27months (range 7-36months). There was no significant difference in distant metastasis-free survival (DMFS) between PR/CR group and PD/SD group (P = 0.0914), while CTC low-R group had a worse DMFS than CTC high-R group (P = 0.0199). In PR/CR subgroup, patients with CTC low-R showed a lower DMFS compared with those with CTC high-R (P = 0.0159). However, in PD/SD subgroup, there was no significant difference in DMFS between CTC low-R and CTC high-R group (P = 0.7521). In terms of assessing response to NCT, CTC change or RECIST classification alone had an AUC of 0.533 (95% CI 0.277-0.790) and 0.700 (95% CI 0.611-0.789), respectively. When combining the two, the AUC slightly increased to 0.713 (95% CI 0.532-0.895). The change of CTC number during NCT has a potential to serve as a supplement to RECIST in the assessment of NCT efficacy and the prognosis of LABC patients.

Prophylactic Lymphovenous Anastomosis Performed during Complete Lymphadenectomy Does Not Increase Risk of Distant Metastasis

BACKGROUND: Lymphovenous bypass (LVB) is the preferred surgical treatment for extremity lymphedema after complete lymph node dissection (CLND). Prophylactic LVB is most frequently performed after CLND for malignancies including breast, gynecologic, and skin cancers. A serious concern with LVB is facilitation of cancer metastasis. PURPOSE: The purpose of this study was to compare rates of distant-metastasis free survival (DMFS) and relapse-free survival (RFS) between patients who underwent LVB during CLND for grossly metastatic disease and patients who underwent CLND only. To our knowledge, this is the first prospective study to evaluate the impact of prophylactic LVB on DMFS and RFS in cancer. METHODS: This is a prospective review of skin cancer patients who underwent axillary/inguinal CLND with or without LVB, between 2014 and 2020. To reduce inter-surgeon differences, all cases were performed by a single, high-volume surgeon at a tertiary hospital. Patients were excluded if they had non-melanoma cancers, stage IV disease before CLND, or follow-up time <180 days. Each LVB patient matched with a control patient based on follow-up times and cancer stage. Collected data include patient demographics, recurrence rate, immunotherapy status, and follow-up time. RESULTS: A total of 79 patients were reviewed. Fifty-two patients had various skin cancers and underwent prophylactic LVB after CLND (LVB group). Among all LVB patients, 42 had melanomas, and among them, 27 met inclusion criteria. Likewise, 27 patients who underwent CLND only (control group) were also included in this study. The two groups were similar in age, sex, follow-up time, and total nodes removed during CLND. Follow-up times were on average 16.24 ± 6.92 and 18.14 ± 9.41 months for the LVB and control groups, respectively (P = 0.40). Average number of lymph nodes removed during CLND were 16.41 ± 9.57 and 17.46 ± 15.43 in the LVB and control groups, respectively (P = 0.71). The LVB group had larger metastatic tumors in lymph nodes at 36.05 ± 40.91 mm compared with the control group at 4.40 ± 7.22 mm (P = 0.0021). The LVB group had lower rates of lymphedema at 41% compared with the control group at 85% (P = 0.0007). There were no differences in DMFS (P = 0.26) and RFS (P = 0.21) between the LVB and control groups based on Kaplan-Meier curves of survival outcomes within 1.5 years (547 days) of treatment. Melanoma recurrence rates were 48% in the LVB group and 37% in the control group (P = 0.41). Immunotherapy usage was more common in the LVB group at 92.59% compared with the control group at 59.26% (P = 0.0042). Rates of failed immunotherapy (ie, melanoma progression or recurrence during treatment) were 56% and 50% for the LVB and control groups, respectively (P = 0.71). Patients who failed immunotherapy had higher rates of melanoma recurrence at 86.36% than patients who did not at 26.32% (P < 0.0001). CONCLUSIONS: Prophylactic LVB during CLND does not impact DMFS and RFS in melanoma, which is potentially applicable to all cancers considering the extremely aggressive nature of melanoma. LVB is highly efficacious in treating lymphedema, especially given that the LVB group had considerably larger tumors in affected lymph nodes.

Comparison of radical prostatectomy and external beam radiotherapy in high-risk prostate cancer.

PurposeWe evaluated clinical outcomes of high-risk prostate cancer patients receiving external beam radiotherapy (EBRT) or radical prostatectomy (RP).Materials and MethodsPatients were classified as high-risk prostate cancer and received definitive treatment between 2005 and 2015. Patients with previous pelvic radiotherapy, positive lymph node or distant metastasis were excluded. The primary outcomes were prostate cancer-specific survival (PCSS) and distant metastasis-free survival (DMFS). ResultsOf 583 patients met the inclusion criteria (77 EBRT and 506 RP), the estimated 10-year PCSS was 97.0% in the RP and 95.9% in the EBRT (p = 0.770). No significant difference was seen in the DMFS (p = 0.540), whereas there was a trend in favor of RP over EBRT in overall survival (OS) (p = 0.068). Propensity score matching analysis with confounding variables was done, with 183 patients (66 EBRT and 117 RP) were included. No significant difference in DMFS, PCSS or OS was found. ConclusionOur data demonstrated similar oncologic PCSS, OS, and DMFS outcomes between EBRT and RP patients.

Abstract PS4-04: Molecular subtyping by BluePrint improves prediction of treatment responses and survival outcomes in patients with discordant clinical and genomic classification

Abstract Background: The risk of distant recurrence gene signature, MammaPrint (MP), together with the molecular subtyping gene signature, BluePrint (BP), stratifies breast tumors into Luminal A, Luminal B, HER2, and Basal subtypes, independent of immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH) expression. In the Neoadjuvant Breast Registry Symphony Trial (NBRST), MP and BP identified patients likely to respond to neoadjuvant treatment with higher accuracy compared to conventional methods. Here, we report 5-year follow up (FU) data in breast cancer (BC) patients from the NBRST registry with discordant clinical and genomic subtyping.Methods: This prospective study enrolled 1072 early-stage BC patients from 2009-2014 who received MP and BP testing. Patients received neoadjuvant therapy following standard of care and consented to 5 years post-surgery FU. IHC determined hormone receptor (HR) status, including ER and PR, and IHC and/or FISH determined HER2 status. Median FU for distant metastasis free survival (DMFS) and overall survival (OS) was 4.6 and 5 years, respectively. Differences in DMFS and OS was assessed by Kaplan Meier analysis and log-rank test.Results: Overall, BP reclassified 22% of tumors into different molecular subtypes compared to IHC/FISH (Table). BP reclassified 17% of ER+HER2- tumors as BP Basal, with higher pathological complete response (pCR) rates compared to ER+/BP Luminal tumors (36% vs. 4%). ER+/BP Basal patients had similar pCR rates as triple negative BC (TNBC)/BP Basal patients (36% vs. 37%) following neoadjuvant treatment, and pCR correlated with improved survival outcomes. The 5-year DMFS and OS probabilities were lower in ER+/BP Basal patients compared to TNBC/BP Basal patients and were substantially lower compared to ER+/BP Luminal patients (P &amp;lt; 0.001). There were 106 HR-HER2+ patients, of whom BP reclassified 23.6% to Basal and 2.8% as Luminal B; the remaining 73.6% were confirmed HER2 by BP. The 5-year DMFS and OS probabilities were worse in HER2+/BP Basal patients compared to HER2+/BP HER2 patients. Of 142 triple positive (TP, ER+PR+HER2+) patients, BP classified 55% as Luminal, 39% as HER2, and 6% as Basal, with higher pCR rates observed in BP Basal and BP HER2 tumors compared to BP Luminal. The 5-year DMFS and OS probabilities were substantially lower in TP/BP Basal patients compared to TP/BP HER2 and TP/BP Luminal patients (P &amp;lt; 0.05 and P &amp;lt; 0.04). Of clinical HER2+ patients (HR+ or HR-) that received pertuzumab, patients that reclassified as BP Basal had worse OS compared to BP HER2 patients (P &amp;lt; 0.04).Conclusion: ER+HER2- and HER2+ patients that reclassified as BP Basal are more likely to achieve pCR and have improved survival, demonstrating the clinical utility of BP in the neoadjuvant setting. These patients may benefit from optimized chemotherapy used for TNBC, including novel emerging treatments such as PD-1 and PARP1 inhibitors, in addition to HER2-targeted therapy. Furthermore, HER2+ tumors that were confirmed HER2 by BP may have high response rates to regimens containing TDM-1. Lastly, BP identified a subgroup of triple positive BC patients, who reclassified as BP Luminal, that may avoid overtreatment. Overall, molecular subtyping using MP and BP is more accurate in stratifying patients and predicting treatment responses and 5-year disease outcomes than conventional methods and thus, facilitates successful treatment decisions. Clinical subtypeFrequency of BP classificationBluePrint subtypepCR%5-yr DMFS (95% CI)5-yr OS (95% CI)TNBC (n=236)0.42% (1/236)Luminal A100% (1/1)N/AN/A2.54% (6/236)Luminal B16.67% (1/6)N/AN/A1.27% (3/236)HER233.33% (1/3)N/AN/A95.76% (226/236)Basal36.73% (83/226)100% (pCR)100% (pCR)60.5% (50.5-69.1)(non-PCR)64.3%(52.1-71.2) (non-PCR)ER+HER2- (n=520)28.84% (152/520)Luminal A1.97% (3/152)91.1% (84.0-95.2)94.6% (88.3-97.6)52.37% (276/520)Luminal B5.43% (15/276)75.2% (69.0-80.4)84.5% (79.0-88.7)1.33% (7/520)HER214.29% (1/7)N/AN/A17.46% (92/520)Basal35.9%(33/92)84.1% (67.8-92.5) (pCR)86.3% (70.1-94.1) (pCR)54.6% (42.0-65.5) (non-pCR)57% (43.7-68.2) (non-pCR)HR-HER2+ (n=106)2.83% (3/106)Luminal B66.67% (2/3)100%100%73.59% (78/106)HER269% (54/78)82.8% (69.9-90.5)88.6% (76.0-94.8)23.58% (25/106)Basal40% (10/25)79.0% (52.5-91.7)79.0% (52.5-91.7)Triple Positive (n=142)12.68% (18/142)Luminal A22.22% (4/18)88.8% (76.5-94.8)94.5% (83.8-98.2)42.25% (60/142)Luminal B11.67%(7/60)38.73% (55/142)HER244.44% (24/55)87.5% (72.0-94.7)97.9% (83.8-98.2)6.34% (9/142)Basal55.56%(5/9)62.5% (22.9-86.1)70.0% (22.5-91.8)HER2+ (HR+ or HR-)treated with pertuzumab (n=105)28.6%(30/105)Luminal37% (11/30)84.7% (63.8-94.1)92.2%(71.8-98.0)57%(60/105)HER282% (49/60)91.4% (78.3-96.8)92.9%(79.2-97.7)14%(15/105)Basal40% (6/15)66.0%(31.1-86.3)64.0% (29.1-85.1) Citation Format: Pat Whitworth, James Pellicane, Jr, Paul Baron, Peter Beitsch, Laura Lee, Michael Rotkis, Angela Mislowsky, Carrie Dul, Charles Nash, Bichlien Nguyen, Mary Murray, Paul Richards, Mark Gittleman, Stephanie Akbari, Shiyu Wang, Andrea Menicucci, Erin B Yoder, Lisa Blumencranz, William Audeh. Molecular subtyping by BluePrint improves prediction of treatment responses and survival outcomes in patients with discordant clinical and genomic classification [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-04.

Intensity-Modulated Radiation Therapy May Improve Survival and Local Tumor Control in Resected Tracheo-Bronchial Adenoid Cystic Carcinoma: A Retrospective Study of 65 Cases

The evidence about survival benefit of radiation therapy (RT) in resected tracheo-bronchial adenoid cystic carcinoma (TACC) is limited. Advanced intensity-modulated radiation therapy (IMRT) technique could improve tumor dose conformality and reduce normal tissue exposure, which would result in a higher rate of local control and a longer survival time compared with conventional RT. This study aimed to evaluate the impact of postoperative IMRT on survival of TACC patients. Patients with TACC treated with surgery and adjuvant radiotherapy in our institution between 1976 and 2016 were retrospectively reviewed. The adjuvant RT was given when the margin was positive or the tumor was close to the resection margin. Patients were dichotomized into IMRT or non-IMRT group. The overall survival (OS), loco-regional recurrence free survival (LRFS), and distant metastasis free survival (DMFS) were calculated from the date of diagnosis. Cox regression was used to identify factors associated with survival and adjust for covariates (P value <0.1 in the univariate analysis). A total of 65 patients were eligible, including 30 with IMRT and 35 with non-IMRT. Patients in the IMRT group had a higher proportion of pathologic N1 stage (30.0% vs. 8.6%, P = 0.058). Other baseline characters (age, sex, tumor location, T stage (T1-2 vs. T3-4), and Charlson/Deyo comorbidity score) were well balanced. The 5- and 10-year OS of the IMRT group were 89.4% (95%CI: 70.6%-96.5%) and 83.9% (95%CI: 61.4%-93.8%), which were significantly superior to those of the non-IMRT group (78.2 % [95%CI: 59.4%-89.0%] and 50.3 % [95%CI: 30.2%-67.4%]; P = 0.031). IMRT was associated with significantly improved 5- and 10-year LRFS in comparison with non-IMRT (5-year: 96.3% [95%CI: 76.5%-99.5%] vs. 68.7% [95%CI: 49.4%-81.9%]; 10-year: 89.9% [95%CI: 63.6%-97.5%] vs. 44.4% [95%CI: 22.4%-64.3%]; P = 0.002). Only 2 of 30 patients (6.6%) developed loco-regional recurrence after IMRT, whereas 14 of 35 (40.0%) failed locally in the non-IMRT group. No difference in DMFS was observed between IMRT and non-IMRT groups (P = 0.680). There were no statistical differences in OS as for RT dose or adjuvant chemotherapy. Multivariable analysis identified IMRT as an independent favorable factor of OS (HR = 0.31, 95% CI: 0.11-0.85, P = 0.022) and LRFS (HR = 0.18, 95% CI: 0.04-0.81, P = 0.025) after adjusting for T stage (P = 0.100 on univariable analysis) and tumor size (P = 0.033). IMRT was an effective treatment which might confer superior local control and survival benefit in the setting of postoperative TACC.

70-Gene Signature as an Aid to Treatment Decisions in Early Breast Cancer: Updated Results MINDACT

Background: The MINDACT trial showed excellent 5-year distant metastasis-free survival (DMFS) of 94·7% (95%CI 92·5-96·2) in clinical high (C-High)/genomic low (G-Low) risk patients who did not receive chemotherapy. Long-term follow-up is presented. Methods: 6693 patients were enrolled 2007 to 2011. We reassessed DMFS rate at 5 years in C-High/G-Low patients not receiving chemotherapy (n=644) (primary analysis), updated DMFS and overall survival in C-High/G-Low patients receiving chemotherapy or not (n=749 and 748, respectively) (secondary analysis), and examined a potential age effect ( 50y) for women with HR+/HER2- disease. Findings: At a median follow-up of 8·7 years, the updated 5-year DMFS rate for C-High/G-Low patients receiving no chemotherapy is 95·1% (95%CI 93·1-96·6), above the predefined non-inferiority boundary of 92%, proving MINDACT as a positive de-escalation trial.The 5-year and 8-year outcome of C-High/G-Low patients show a respective 0·9% (SE ±1·1) 2·6% (SE ±1·6) difference in DMFS for chemotherapy versus no chemotherapy (HR 0·66; 95%CI 0·48-0·92), without differences in overall survival (95·7% vs 94·3%).The same comparisons confined to HR+/HER2- disease (91% of patients) generate different gain estimates from chemotherapy administration for DMFS according to age: 5% (SE ±2·8%) in women ≤50 years versus 0·2% (SE ±2·3%) in women > 50 years. Interpretation: The clinical utility of a low risk 70-gene signature for foregoing adjuvant chemotherapy in the presence of a high clinical risk (and up to 3 positive nodes) remains proven. In C-high/G-low patients > 50 years chemotherapy did not improve outcome across the whole follow-up trajectory. At longer follow-up in younger women, while underpowered, a clinically relevant benefit of about 5% was observed, possibly due to chemotherapy-induced ovarian function suppression, and should be part of informed, shared decision-making. Trial Registration: ClinicalTrials.gov number, NTC00433589; EudraCT number, 2005-002625-31. Funding Statement: Funded by the European Commission Sixth Framework Programme and other grants. Declaration of Interests: None to declare. Ethics Approval Statement: All patients gave written informed consent. The ethics committees of all participating sites approved the study, which involved collaboration of seven member groups under the Breast International Group umbrella.

Clinical validation of an immunohistochemistry-based CanAssist-Breast test for distant recurrence prediction in hormone receptor-positive breast cancer patients.

CanAssist‐Breast (CAB) is an immunohistochemistry (IHC)‐based prognostic test for early‐stage Hormone Receptor (HR+)‐positive breast cancer patients. CAB uses a Support Vector Machine (SVM) trained algorithm which utilizes expression levels of five biomarkers (CD44, ABCC4, ABCC11, N‐Cadherin, and Pan‐Cadherin) and three clinical parameters such as tumor size, grade, and node status as inputs to generate a risk score and categorizes patients as low‐ or high‐risk for distant recurrence within 5 years of diagnosis. In this study, we present clinical validation of CAB. CAB was validated using a retrospective cohort of 857 patients. All patients were treated either with endocrine therapy or chemoendocrine therapy. Risk categorization by CAB was analyzed by calculating Distant Metastasis‐Free Survival (DMFS) and recurrence rates using Kaplan‐Meier survival curves. Multivariate analysis was performed to calculate Hazard ratios (HR) for CAB high‐risk vs low‐risk patients. The results showed that Distant Metastasis‐Free Survival (DMFS) was significantly different (P‐0.002) between low‐ (DMFS: 95%) and high‐risk (DMFS: 80%) categories in the endocrine therapy treated alone subgroup (n = 195) as well as in the total cohort (n = 857, low‐risk DMFS: 95%, high‐risk DMFS: 84%, P < 0.0001). In addition, the segregation of the risk categories was significant (P = 0.0005) in node‐positive patients, with a difference in DMFS of 12%. In multivariate analysis, CAB risk score was the most significant predictor of distant recurrence with hazard ratio of 3.2048 (P < 0.0001). CAB stratified patients into discrete risk categories with high statistical significance compared to Ki‐67 and IHC4 score‐based stratification. CAB stratified a higher percentage of the cohort (82%) as low‐risk than IHC4 score (41.6%) and could re‐stratify >74% of high Ki‐67 and IHC4 score intermediate‐risk zone patients into low‐risk category. Overall the data suggest that CAB can effectively predict risk of distant recurrence with clear dichotomous high‐ or low‐risk categorization.

1070P - Evaluate the role of induction chemotherapy in the treatment of stage II nasopharyngeal carcinoma in intensity modulated radiotherapy era

Background: While the combined modality treatment of concurrent chemoradiotherapy (CCRT) with or without adjuvant chemotherapy has now been accepted as the standard treatment for advanced Nasopharyngeal carcinoma (NPC), induction chemotherapy +concurrent chemoradiotherapy (ICRT) is commonly used as well. The prognosis of II NPC patients is favorable. We should be more mindful to living quality during/after treatment, length of hospital stay, treatment cost and so forth. Therefore, the purpose of this study is to contrast prognosis of stage II NPC patients underwent the following two treatment modalities: ICRT vs CCRT. Methods: 173 patients with American Joint Committee on Cancer 7th stage II NPC are included and divided into two groups: ICRT and CCRT. Induction chemotherapy consisted of 1 to 3 cycles of cisplatin plus fluorouracil or paclitaxel plus cisplatin. Concurrent chemotherapy includes cisplatin only. We retrospectively assess overall survival (OS), progression-free survival (PFS), locoregional free survival (LRFS) and distant metastasis free survival (DMFS). Results: With a median follow up of 64.7 months, no significant differences are found in grade 3–4 hematologic toxicity, liver dysfunction and renal impairment between ICRT and CCRT groups. Univariable analyses show adding induction chemotherapy to CCRT significantly decreases 5-year OS (87.9% vs 95.5%, P = 0.033), PFS (74.0% vs 86.1%, P = 0 .035), LRFS (80.0% vs 91.2%, P = 0.016), but there is no statistically significant difference in DMFS (87.1% vs 94.7%, P = 0.095). In multivariable analyses, we find the consistent results that induction chemotherapy is a negative factor associated with OS (HR of death =3.768, 95% CI = 1.117 to 12.709; P = 0.032), PFS (HR of progression = 2.156, 95% CI = 1.060 to 4.386; P = 0.034), LRFS (HR of locoregional relapse = 2.435, 95% CI = 1.009 to 5.874; P = 0.048) and also DMFS (HR of metastasis = 2.873, 95% CI = 1.005 to 8.211; P = 0.049), in stage II NPC patients. Conclusions: In present study, we find that induction chemotherapy causes deleterious effect on stage II NPC patients. However, this is a retrospective study and the adverse effects of induction chemotherapy has not been previously reported. It warrants further investigation. Legal entity responsible for the study: Zhejiang Cancer Hospital. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.