bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between baseline parameters and overall survival in patients with advanced melanoma treated with ipilimumab.
Authors: Geukes Foppen Marnix Heimen , Jordanova Ekatarina S. , Van Thienen Johannes V. , Punt Simone , Van De Wiel Bart , Haanen John B. A. G. , Blank Christian U. 
Published: September 2018

9572 Background: Checkpoint inhibitors (IT) have revolutionized treatment options for patients (pts) with advanced melanoma. Recently, we proposed a framework of 7 parameters (PM) describing requirements for a sufficient anti-tumor immune response (the “cancer immunogram”). In a first analysis we tested pts from our ipi cohort for outcome. Using this framework pts benefitting the most from treatment with ipi might be selected upfront, and in the future also from other checkpoint inhibitors. Methods: Using Kaplan-Meier- and Cox-regression-analysis correlations between 6 of these PM at baseline and overall survival (OS) were investigated in a single center cohort of pts treated with 3 mg/kg ipi for metastatic melanoma. Results of the 7thPM are currently being finalized. Results: PM assessed were: LDH (≤ULN vs > ULN), erythrocyte sedimentation rate (ESR,≤ULN vs > ULN), absolute lymphocyte count (ALC, < 1000/mm3 vs ≥1000/mm3) and IHC on tumor material for CD8+ T-cell infiltration ( < median vs ≥median), PD-L1 expression ( < 1% vs ≥1% positive cells) and MHC-class I expression (loss vs weak/positive). We analyzed 179 pts treated with ipi between 2010 and 2013. Median age was 55 years (19–88) and 61% of pts were male. Minimum follow-up of pts alive was 42 months(mo). Data were available as follows:177 cases LDH, 159 ALC/ESR, 118 PD-L1, 99 CD8 and 68 MHC-class I. Median OS was 7.1 mo. In univariable analysis LDH (HR 2.5, 95%CI 1.8-3.5), ALC (HR 1.6, 95%CI 1.1-2.4), ESR (HR 2.4, 95%CI 1.5-3.8) and CD8 (HR 1.8 95%CI 1.2-2.8) were significant for OS ( p< 0.01). Pts with all 4 favorable PM had a median OS of 25.1mo(95%NR), pts with 3 PM 15.8 mo(95%CI 7.0-24.7), 2 PM 8.1 mo(95%CI 1.0-15.3), 1 PM 4.8 mo(95%CI 3.3-6.3) and no favorable PM 1.7 mo(95%CI 0–4.9). In multivariable analysis LDH(HR 2.4,95%CI 1.5-4.0) and CD8(HR 1.7,95%CI 1.1-2.8) were the only independent PM. Pts with a normal LDH and high CD8 had a median OS of 15.8 mo(95%CI 9.5-22.2) vs 3.8 mo(95%CI 1.8-5.7) for pts that did not ( p< 0.01). Conclusions: In conclusion, low values of baseline LDH and high values of CD8 are the strongest PM associated with a favorable outcome in pts with advanced melanoma, treated with ipi. The other PM added low effect on the pts outcome upon ipi.
Interim analysis of survival outcomes in a prospective cohort evaluating a prognostic 31-gene expression profile (GEP) test for melanoma.
Authors: Hsueh Eddy C. , DeBloom James R. , Lee Jonathan H. , Sussman Jeffrey J. , Slingluff Craig L. , McMasters Kelly 
Published: September 2018

9573 Background: DecisionDx-Melanoma has been validated as an accurate prognosticator of cutaneous melanoma (CM) metastasis risk. The GEP test classifies CM pts as Class 1 (low risk) or Class 2 (high risk). Interim survival analysis from two clinical registry studies (NCT02355574/NCT02355587) designed to prospectively evaluate outcomes in pts for whom the GEP test was performed is described. Methods: Eleven US dermatologic and surgical centers participated in the IRB-approved protocols. Physicians enrolled CM pts who were ≥16 years old and had successful GEP test results. Endpoints of recurrence-free (RFS), distant metastasis-free (DMFS) and melanoma-specific survival (MSS) were assessed using Kaplan-Meier and Cox regression analysis. As an interim analysis at year 3 of an expected 5-year study, the critical alpha level (p-value) was 0.01. Results: At the time of data extraction, 322 pts were accrued and completed at least one follow-up visit. Median age was 58 years (range 18-87), median Breslow thickness (BT) was 1.2mm, 55% were male, 20% (58/296) were ulcerated, and 15% (36/237 biopsied) had a positive sentinel lymph node (SLN). Median follow-up time was 1.5 years for pts without a recurrence. Of 25 recurrent cases, 80% (20/25) were Class 2 and 40% (10/25) were SLN-positive. Two percent of Class 1 pts had a recurrence compared to 6% (12/201 biopsied) of SLN-negative pts. Of the SLN-negative pts who recurred, 75% (9/12) were called Class 2. Combined GEP and SLN risk prediction identified 88% (21/24) of recurrences. Kaplan-Meier event rates for each class are shown in the table. In Cox multivariate analysis, BT and GEP Class 2 were significant predictors of recurrence (p<0.01 for each). Conclusions: Results of this analysis show that the GEP test provides prognostic information that complements conventional staging and significantly enhances identification of high risk CM pts, consistent with reported validation studies.The results support use of the test for guiding surveillance decisions and enrollment of CM pts in clinical trials. Clinical trial information: NCT02355574, NCT02355587. [Table: see text]
Primary melanoma histologic subtype (HS) impacts melanoma specific survival (MSS) and response to systemic therapy.
Authors: Lattanzi Michael , Lee Yesung , Robinson Eric Michael , Weiss Sarah A. , Moran Una , Simpson Danny , Shapiro Richard L. , Berman Russell S. , Pavlick Anna C. , Wilson Melissa , Kirchhoff Tomas , Zhong Judy , Osman Iman 
Published: September 2018

9577 Background: Unlike other solid tumors, the impact of primary HS on melanoma survival and response to systemic therapy is not well studied. Nodular melanoma (NM) has a worse prognosis than superficial spreading melanoma (SSM), which is usually attributed to thicker primary tumors. Herein, we examine the hypothesis that HS might have an impact on MSS independent of thickness and that NM and SSM exhibit different mutational landscapes that associate with response to checkpoint inhibitor immunotherapy (IT) and BRAF targeted therapy (TT) in the metastatic setting. Methods: Primary NM and SSM patients prospectively enrolled at NYU (2002 - 2016) were compared to the most recent SEER cohort (1973 - 2012) and analyzed with respect to MSS. Next-Generation Sequencing (NGS) was performed on a subset of matched tumor-germline pairs, allowing a comparison of the mutational landscape between NM and SSM. In the metastatic setting, survival analyses were used to compare outcomes and responses to treatment across HS. Results: The NYU cohort of 1,621 patients with either NM (n = 510) or SSM (n = 1,111) was representative of the analogous SEER cohort (21,339 NM, 97,169 SSM), with NM presenting as thicker, more ulcerated, and later stage (all p < 0.001). Among the NYU cohort, NM was found to have lower rates of TIL (p = 0.047), higher mitotic index (p < 0.001), and higher rates of NRAS mutation (p < 0.001). In multivariate Cox models, NM was a significant predictor of worse MSS, independent of thickness and stage (p = 0.01). NM had a significantly lower mutational burden across the exome (p < 0.001). Some of the most under-mutated genes noted in NM were NOTCH4, BCL2L12 and RPS6KA6 (all p < 0.01). Among patients treated with TT (n = 56), NM remained a significant predictor of worse MSS (p = 0.004). However, there was no difference in response to IT. Conclusions: NM and SSM show divergent mutational patterns which may contribute to their different clinical behaviors and responses to BRAF targeted therapy. More studies are needed to better understand the key molecular and cellular processes driving such differences. Integration of HS data into prospective clinical trial reporting is needed to better assess its impact on response to treatment.
Explanation model using pathological data for treatment outcome of patients with early-stage breast cancer with hormonal receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative.
Authors: Prasongsook Naiyarat 
Published: September 2018

e12006 Background: The decision to initiate adjuvant chemotherapy for early-stage breast cancer patients with HR+ and HER2- is still unclear. Although the 21-gene Recurrence Score (RS) assay is a validated testing and becomes an emerging decision-making tool; it is still controversial guidance on adding adjuvant chemotherapy for patients with intermediate RS. This study aimed to develop the explanation model by using pathological information for prediction of the best outcome from adjuvant systemic treatment in these patients.Methods: Early-stage breast cancer patients with HR+, and HER2- who underwent complete resection registered within electronic medical record from 2003 to 2013 were included. Patient’s characteristics and pathological information were collected and analyzed. Univariate and multivariate analysis were conducted by using stepwise logistic regression. The explanation model was explored by using association between multivariate models and overall survival (OS).Results: 236 patients who underwent complete surgery treatment were included. 121 patients (51%) were treated with sequential adjuvant treatment, and 115 patients (48%) with anti-hormonal therapy alone. Clinicopathological parameters between two groups were demonstrated in Table1. Tumor size (≥2 – 5 cm), Estrogen receptor-negative/ Progesterone receptor-positive (ER-/PgR+), and Ki-67 expression were statistically significant multivariate independent prognostic factors for OS. When we adjusted for tumor size, HR status, and Ki-67 expression, the explanation model predicted 10-year OS was 99.2% for patients with sequential adjuvant treatment, whereas 89.5% for patients with adjuvant anti-hormonal alone (difference: 9.7%); p-value = 0.01.Conclusions: We found substantial discordance in 10-year OS benefit between early-breast cancer patients with HR+, HER2- with sequential adjuvant therapy and adjuvant hormonal therapy alone. Adjuvant chemotherapy should be considered in early-breast cancer patients with 2-3 cm in tumor size, ER-/PgR+, and Ki 67 expression.
A clinicopathological prediction model for recurrence in patients with early-stage hormone-receptor-positive, HER2-negative breast cancer at King Chulalongkorn Memorial Hospital.
Authors: Uttamapinan Suleepon , Iampenkhae Kroongpong , Rattananupong Thanapoom , Poovorawan Nattaya , Sriuranpong Virote , Parinyanitikul Napa 
Published: September 2018

e12015 Background: Genetic recurrent score has been increasingly applied in combination with clinicopathology for predicting recurrence and guiding the potential role of adjuvant chemotherapy in patients with early breast cancer. However, lack of accessibility limits its use for clinical practice especially in developing countries. Our study aims to formulate model for predicting risk of recurrence in patients with hormone-receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. Methods: Five hundred and twenty nine HR-positive, HER2-negative early breast cancer patients who were diagnosed during 2005 to 2015 in King Chulalongkorn Memorial Hospital were retrospectively reviewed. All potentially clinicopathologic prognostic factors for recurrence were analyzed using multivariable logistic regression. Results: Ninety eight HR-positive, HER2-negative early breast cancers developed distant recurrences after a median follow-up of 65.7 months (IQR, 41.2 - 92.3). There was no difference among recurrent and non-recurrent groups in term of age and menopausal status. However, greater number of patients in non-recurrent group had earlier stage (stage I or II). Most of patients in both groups received hormonal therapy, while more patients in the recurrent group received adjuvant (82.7% vs. 70.8%; P = 0.017) and neoadjuvant chemotherapy (35.1% vs. 11.2 %; P < 0.001). From multiple logistic regression using clinical and pathologic variables, lymphovascular invasion (LVI), percentage of Ki-67, and tumor size were independent predictors of recurrence (OR 3.04; P < 0.001, OR 1.02; P = 0.001, and OR 1.18; P= 0.05, respectively). The prediction model for 10-year recurrent risk appears as “log (odd) = - 3.535 + 0.020 (percentage of Ki-67) + 0.165 (Tumor size in cm) + 1.111 (LVI)”. Probability of recurrence is defined as odd / (1+odd). This model yields a C statistic above 0.7 on validation in independent population. Conclusions: A new clinicopathologic prediction model provides comprehensive recurrent risk estimation for Thai patients with HR-positive, HER2-negative early breast cancer.
A comparative analysis of clinicopathological characteristics and disease-free survival (DFS) outcomes in breast cancer patients: Mammograpghy vs symptomatic diagnosis.
Authors: Karaca Mustafa 
Published: September 2018

e12018 Background: Our goal was to compare clinicopathological characteristics and DFS time among breast cancer patients diagnosed with mammography or symptoms. Methods: This was retrospective analysis of 828 patient files. Diagnosis was done with mammography or symptom,considering the followings:age,menopause,hormone and HER2 receptor,grade,histologic subtype,lymphovascular(LVI) and perineuronal invasion(PNI),adjuvant chemotheraphy,adjuvant herceptin,adjuvant hormone and adjuvant radiotheraphy use.Recurrence dates,locations and last appointment dates were noted. Results: Breast cancer was detected by mammography in 324 patients vs by sysmptom in 504.The difference in most cases between these two methods were significant,and respectively:positive ALND 30% vs 53.7% p=0.0001,LVI 13.7% vs 31.6% p=0.0001,PNI 7.2% vs 18.1% p=0.0001,adjuvant chemo 67% vs 85% p=0.0001,adjuvant hormone use 87.3% vs 82% p=0.001.However, recurrence rates did not differ sigificantly among two groups 12% vs 12.6% p=0.4.The median follow-up and DFS time was 48 and 37 months,respectively.Prognostic parameters were also analyzed.Pathologic staging p=0.002,PNI p=0.027,LVI p=0.0001,hormone receptor status p=0.0001,triple negativity p=0.016,luminal A group p=0.048 were found statistically significant on DFS.Diagnosis with mammography was found to have no statistically significant effect on DFS. Conclusions: Although patients diagnosed with mammography had better prognostic parameters,recurrence rates were similar with symptomatic patients at the time of diagnosis.At survival analysis,recurrence rates were calculated to be similar to those of symptomatic patients’ group.
Relationships of cyclin E with clinical outcome and biomarkers in older women with early operable primary breast cancer.
Authors: Syed Binafsha Manzoor , Green Andrew R. , Morgan Dal , Ellis Ian O. , Hunt Kelly , Keyomarsi Khandan , Cheung Kwok-Leung 
Published: September 2018

e12031 Background: Cyclin E is one of the factors responsible for transition from G1 to S phase of cell division. Cytoplasmic cyclin E has recently been shown to be associated with the greatest risk of breast cancer recurrence (Hunt KK et al. Clin Cancer Res. 2016 Nov 23). This study aimed to analyse intracellular relationships of cyclin E with clinical outcomes and with other biomarkers in a specific patient population. Methods: Over 37 years (1973-2010), 1,758 older (≥70 years) women with early operable (<5cm) primary breast cancer were managed in a dedicated clinic in Nottingham. Of these 813 patients underwent primary surgery and 575 had good quality tumour samples available for tissue microarray construction and immunohistochemical studies of biomarkers. Cytoplasmic expression of cyclin E with or without nuclear expression was considered positive. Results: Cytoplasmic cyclin E expression was associated with poor clinical outcomes on multivariate analysis (see table below). Cytoplasmic cyclin E expression was significantly associated with negative ER(<0.001), PR(p=0.008), CK19(p=0.009) and positive expression of Ki67(p=0.04), p53(p=0.02), CK5(p=0.001), CK17(p=0.04), LKB1(p=0.04), HER3(p=0.03) and HER4(p=0.04). No correlation was found with HER2, BRCA2, CK5/6, CK18, EGFR, CD44, MDM2, MDM4, E-Cadherin and MUC1. Conclusions: Cytoplasmic cyclin E is associated with poor clinical outcome and biomarkers of poor prognostic significance in older population with breast cancer. Cyclin E may serve as a potential therapeutic target in future. [Table: see text]
Trastuzumab-related cardiotoxicity in patients with non-limiting cardiac comorbidity.
Authors: Martinello Rossella , Becco Paolo , Vici Patrizia , Airoldi Mario , Del Mastro Lucia , Garrone Ornella , Barone Carla , Pizzuti Laura , D'Alonzo Alessia , Bellini Elisa , Milani Andrea , Bonzano Alessandro , Montemurro Filippo 
Published: September 2018

e12043 Background: Significant and symptomatic cardiac comorbidity (CC) is a contraindication to adjuvant trastuzumab (T) in breast cancer patients (pts). However, some pts with asymptomatic, non-limiting CC and normal baseline left ventricular ejection fraction (LVEF) receive T in the clinical practice. We sought to describe the tolerability of T in these pts. Methods: Retrospective analysis of pts with baseline asymptomatic non-limiting CC receiving adjuvant T with chemotherapy (CT) at 6 Institutions between Jul 2006 and Jan 2016. Results: Thirty-seven patients HER2-positive, operable BC at high risk of relapse BC were studied. Median age was 64y (range 36-82, 80% post-menopausal), median baseline LVEF was 61% (range 50-85%) and median BMI 26 (18-42, obesity 22%). Thirteen patients (35%) received T with adjuvant anthracycline and taxane-based, 19 (51%) taxane-based and 3 (8%) other adjuvant CT regimens (13 pts sequential, 22 pts concomitant with CT) and 2 (5%) with endocrine therapy. Prior non-limiting CC was ischemic heart disease (35%), valvular disease (30%), atrial fibrillation (19%), conduction disorders (13%), aortic aneurism (3%), and other (19%). Nine (29%) pts experienced TRC: congestive heart failure (1 pt, 3%), LVEF reduction (6 pts, 16%) and rhythm disturbances (1 pt, 3%). TRC occurred in pts with ongoing multiple cardiovascular risk factors (i.e. obesity and hypertension). Seven pts discontinued T because of TRC (19%), 5 permanently (14%) and 2 temporarily (5%). These latter pts, were able to resume and complete T after TRC resolution. At the end of adjuvant treatment, all pts showed LVEF within normal limits, except one of those who experienced a TRC (last FU value 46 %). Conclusions: This is the first analysis of TRC in pts receiving adjuvant T in the presence prior non-limiting CC. Despite the small size, our analysis shows that T is feasible in these pts and most of the TRC events were reversible at T withdrawal. Caution is needed in pts with significant ongoing cardiovascular risk factors, but when adjuvant T is deemed beneficial on breast cancer outcomes, non-limiting CC should not preclude treatment.
Adherence and persistence to adjuvant hormonal therapy in early stage breast cancer patients: A population-based retrospective cohort study in Israel.
Authors: Sella Tal , Chodick Gabriel 
Published: September 2018

e12051 Background: Adjuvant hormonal therapy has been consistently proven to improve multiple outcomes in early breast cancer. Nonetheless, data on rates of adherence and persistence with therapy outside West Europe and North America are scarce. We assessed the adherence and persistence with adjuvant hormonal in a retrospective population based cohort of breast cancer survivors in Maccabi Health Services (MHS), Israel. Methods: We identified women who were diagnosed with breast cancer and initiated adjuvant hormonal therapy between January 2000 and November 2008. Subjects were followed retrospectively from first dispensed tamoxifen or aromatase inhibitor (AI) and up to the earliest of the following events: disease recurrence (indicated by surgery, radiotherapy, chemotherapy or other related therapies), leaving MHS, death, or completion of 5 years of treatment. Discontinuation of therapy was defined as a 180-day or longer treatment gap. Adherence with therapy was assessed using proportion of days covered (PDC) during follow-up period. Survival analysis was used to determine the effect of adherence on all-cause mortality. Results: A total of 4178 women with breast cancer were followed for a median 7.8 years. Over 90% of patients received tamoxifen as the initial hormonal agent. Mean PDC was 84% with lower rates associated with younger age, smoking status, comorbidities and year of diagnosis. Residential area did not affect adherence. Differences were not found. Discontinuation of therapy occurred in 23% of study patients. Among persistent patients, 70% were optimally adherent with therapy (PDC>=80%). Association between adherence with therapy and survival is investigated. Conclusions: Adherence to adjuvant hormonal therapy among Israeli breast cancer patients with national health insurance is high in comparison to international reports. Nevertheless, suboptimal adherence was identified among younger (<45y) patients. Because of the efficacy of hormonal therapy in preventing recurrence and death in women with early-stage breast cancer, interventions are necessary to identify and prevent suboptimal adherence among high risk subgroups.
Outcomes related to delayed initiation of anti-HER 2 therapy in pregnant HER2 positive breast cancer patients.
Authors: Oke Oluchi , Warneke Carla L. , Chavez-Mac Gregor Mariana , Milbourne Andrea , Litton Jennifer Keating 
Published: September 2018

e12059 Background: Overexpression of HER2 is associated with aggressive breast cancers. In non-pregnant HER2+ breast cancer patients, anti-HER2 therapy is usually initiated after surgery or in the neoadjuvant setting. However, for pregnant HER2+ breast cancer patients, anti-HER2 therapy must be delayed until after delivery due to fetal toxicity. We describe here the outcomes of pregnant patients with HER2+ breast cancer at a single center. Methods: Twenty-three pregnant HER2+ breast cancer patients were treated between November 1989 to October 2016. Median age at diagnosis was 31.8. (Table 1) We report Kaplan-Meier estimates of OS from diagnosis and PFS from surgery. The effect of time from diagnosis to anti-HER2 therapy (TTH) on OS and PFS from HER2 therapy initiation was assessed using Cox proportional hazards regression models. Results: Seventeen patients received anti-HER2 therapy after delivery, 6 did not – 4 were treated prior to the use of HER2 therapies, and 2 were lost to follow-up. Median TTH was 181 days. All but 3 patients started HER2 treatment within 2 months of delivery. Twenty-one received anthracycline-based chemotherapy during pregnancy. Three patients have died, with all 3 receiving HER2 therapy, but one only at relapse due to diagnosis before routine trastuzumab use. Median follow-up was 3.4 years (range 0.2-16.2 years), and 5-year OS was 80% (95%CI 41-95%). Five patients progressed. Median PFS was 3.1 years (range 0.3-14.2 years), and 5-year PFS was 75% (95%CI 46-90%). Delay of initiation of HER-2 therapy did not appear to be associated with OS or PFS from date of HER-2 therapy initiation (both n = 17, HR 1.01, 95%CI 0.97-1.06, P= 0.52). Conclusions: In this small case series, we did not detect adverse outcomes associated with delaying initiation of anti-HER2 therapy in pregnant patients with HER2+ breast cancer. Larger series are needed to further evaluate this concern. [Table: see text]