bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of time to switch from ipilimumab to anti-PD1 in anti-PD1 efficacy within the French national cohort, MelBase.
Authors: Allayous Clara , Dalle Stéphane , Leccia Marie Thérèse , Aubin Francois , Mortier Laurent , Beylot-Barry Marie- , Saiag Philippe , Dalac-Rat Sophie , Lacour Jean Philippe , Maubec Eve , Descamps Vincent , Guillot Bernard , Lesimple Thierry , De Quatrebarbes Julie , Arnault Jean-Philippe , Stoebner Pierre-Emmanuel , Porcher Raphael , Ballon Alice , Oriano Bastien , Lebbe Celeste 
Published: September 2018

9551 Background: With increasing armamentarium in advanced melanoma management, the impact of various strategies remains to be determined including the importance of time to switch from one treatment to another. We report the impact of time to IPI/APD non-planned switch on APD efficacy in real life patients within MelBase (MB). Methods: MB is a French multicentric biobank dedicated to the prospective follow-up (FU) of unresectable stage III or IV melanoma with 1102 patients included since March 2013. Data were collected (Sept.2016) and analyzed (demography, overall survival (OS), progression-free survival (PFS), response rate, multivariate analysis, safety). Results: 71 patients were treated with IPI/APD sequence. 72% received 4 IPI injections. The median time to switch was 1.7 months (0.36-3). The characteristics at the initiation of APD are: mean age 64 yrs, PS 0-1 80%, elevated LDH 34%, BRAF WT 90%, brain metastasis 25%, ≥ 3 metastatic organ sites (MOS) 49%, median FU 11.9 months, OS 20 months (95%CI:12.6-NR), PFS 3.5 months (95%CI:2.9-6.2). The best overall response was 25%, disease control rate was 54% with a low toxicity profile (17% grade 3/4). In a multivariable analysis, longer time to switch was significantly associated with better OS (adjusted HR 0.38 per 1 more month, 95%CI:0.14-0.93), as well as ECOG 0-1 (aHR 3.11, 95%CI:0.99-9.72) and LDH < ULN (aHR 3.32, 95%CI:1.26-8.75). In addition, the association of time to switch with OS vary significantly according to the number of MOS ( < 3 MOS aHR 0.25, 95%CI:0.10-0.62; ≥3 MOS aHR 0.99 95%CI:0.41-2.39) and AJCC stage (M0/1a/1b aHR 0.06, 95%CI:0.01-0.43 ; M1c aHR 0.77, 95%CI:0.39-1.54). Conclusions: In patients who failed IPI treatment, longer survival after APD was associated to time to switch only in patients with favorable baseline factors. Such results are probably more related to the slow kinetics of the disease than to the delay itself. Our results are different from Blank et al.(ESMO 2016) who tested a planned switch, immediately after 2 IPI perfusions, and showed overall response rate close to IPI+APD association. We are currently conducting a similar study on the reverse sequence (APD/IPI) and the role on IPI efficacy.
The safety and early efficacy of high-dose ipilimumab (IPI) and the combination nivolumab plus ipilimumab (NIVO + IPI) in patients (pts) with uveal melanoma (UM).
Authors: Patel Sapna Pradyuman , Glitza Isabella Claudia , Diab Adi , Amaria Rodabe Navroze , Davies Michael A. , Hwu Patrick , Tawbi Hussein Abdul-Hassan , Hwu Wen-Jen 
Published: September 2018

9554 Background: UM metastases occur in 50% of cases and high-risk pts are identified by a gene expression profile. High-dose IPI is approved for adjuvant (adj) treatment (tx) of cutaneous melanoma and NIVO + IPI for metastatic (met) melanoma, yet the safety and efficacy of high-dose IPI or NIVO + IPI has not been established in UM in the adj or met settings. Methods: We performed a phase I/II trial of IPI for the tx of high-risk & met UM (CA184-187). The study consisted of two arms: an adj arm (AA) & met arm (MA) with two dose levels, 3 mg/kg & 10 mg/kg. Dose-finding proceeded on each arm in a 3 + 3 fashion. Pts received IPI once every 3 weeks for four doses followed by maintenance IPI every 12 weeks (for up to one year in AA). The AA treated pts with a Class 2 gene expression profile. This score imparts a 3-year distant metastasis-free survival (DMFS) of 50%. The primary endpoint for the AA was maximum tolerated dose (MTD) and improvement in 3-year DMFS to 70%. The primary endpoint for the MA was MTD & overall survival. The study was later amended to include a cohort of UM pts treated with combination NIVO + IPI in the standard FDA approved schedule. Results: Ten pts were enrolled on AA, 18 on MA, and 20 on NIVO + IPI. Adverse events (AEs) of any Grade (Gr) related to tx occurred in 80% of pts on AA. Gr 3/4 related toxicities observed in more than one pt were: transaminitis (30%) & pruritus (20%). Of these, 10% of the elevated AST and ALT and 10% of the pruritus occurred during the dose-finding portion of the trial at 3 mg/kg. One pt developed biopsy-proven colitis, and one developed diarrhea. Both were treated with high-dose steroids. One pt developed vasculitis manifesting as temporal arteritis with resultant blindness. AEs of any Gr occurred in 44% of pts on MA. Gr 3/4 toxicities observed in more than one pt were: Fatigue (11%) and Hyperbilirubinemia (11%). Only 1 pt (5.6%) developed Gr 3/4 diarrhea, and this was at the 3 mg/kg dose. In the NIVO + IPI cohort, Gr 3 transaminitis & elevated TSH occurred in 10%. Conclusions: High-dose IPI in UM did not demonstrate new or unexpected toxicities. Similarly, the combination of NIVO + IPI was well-tolerated with no new toxicities. Efficacy data will be presented at the meeting. Clinical trial information: NCT01585194.
Multivariate analysis of prognostic factors among 706 mucosal melanoma patients.
Authors: Lian Bin , Cui Chuanliang , Zhou Li , Song Xin , Zhang Xiaoshi , Wu Di , Chi Zhihong , Si Lu , Sheng Xinan , Kong Yan , Tang Bixia , Mao Li Li , Wang Xuan , Li Si Ming , Dai Jie , Yan Xieqiao , Bai Xue , Zheng Nan , Balch Charles M. , Guo Jun 
Published: September 2018

9569 Background: Mucosal melanoma is rare and associated with extremely poor prognosis. Little is known about its outcome and prognostic analysis. In this study, we evaluated prognostic factors among mucosal melanomas. Methods: The survival rates, Relapse Free Survival (RFS), Overall Survival (OS) and prognostic factors were compared for 706 mucosal melanomas at different anatomical sites. Results: Mucosal melanoma from nasal pharyngeal and oral (268 pts), upper and lower gastrointestinal (GI) (221 pts), gynecological and urological (196 pts) had a similar survival with a 1-y survival rate (88%, 83%, 86%), 2-y survival rate (66%, 57%, 61%), 5-y survival rate (27%, 16%, 20%), respectively. Multivariate analysis revealed that Depth of Invasion (p < 0.001), Lymph node metastases (p < 0.001), Distant metastases (p < 0.001) were three independent prognostic factors for OS among 706 pts. Anatomical site (p = 0.031), Depth of Invasion (p < 0.001), Lymph node metastases (p < 0.001) were three independent prognostic factors for RFS among 543 pts. KPS status, Depth of Invasion, Lymph node metastases, Distant metastases were independent factors for OS among nasal pharyngeal and oral pts. Depth of Invasion, Lymph node metastases, CKIT Mutation were independent factors for RFS among nasal pharyngeal and oral pts. Gender, Lymph node metastases, Distant metastases were independent factors for OS among GI pts. Gender, Depth of Invasion, Lymph node metastases were independent factors for RFS among GI pts. Lymph node metastases, Distant metastases were independent factors for OS among Gynecological and Urological pts. Depth of Invasion, Lymph node metastases were independent factors for RFS among Gynecological and Urological pts. Conclusions: This is the first prognostic analysis for mucosal melanoma with the largest sample size for the first time. with few exceptions, It revealed that Depth of Invasion, Lymph node metastases, Distant metastases were independent prognostic factors for OS, Depth of Invasion and Lymph node metastases were independent prognostic factors for RFS. These results should be incorporated into the establishment of stage system and design of future clinical trials involving patients with mucosal melanoma.
Characterizing the tumor microenvironment (TME) in primary melanomas using multiplex immunohistochemistry (mIHC).
Authors: Gartrell Robyn Denise , Marks Douglas Kanter , Hart Thomas , Stack Edward , Lu Yan , Esancy Camden , Gerard Camille , Davari Danielle Rose , Jia Dan Tong , Armenta Paul , White-Stern Ashley , El Asmar Margueritta , Blake Zoe , Fu Yichun , Horst Basil , Saenger Yvonne M. ,   Melanoma Mantra Project
Published: September 2018

9580 Background: Biomarkers are needed in primary melanoma to risk stratify for adjuvant trials. High levels of infiltrating cytotoxic (CD8+) T lymphocytes (CTLs) and low levels of CD68+ macrophages (MΦ) may correlate with prolonged survival but quantification methods are not standardized for clinical practice. HLA-DR is a marker of MΦ activation not expressed by suppressor myeloid cells. A novel pathology technique using mIHC allows for quantitative and spatial analysis of immune cell subsets. Methods: In a pilot set of stage II/III primary melanomas from Columbia University Medical Center (n = 94), clinical follow up is available for 51 cases. 32 had no evidence of recurrence at last follow up (minimum 2 years) while 19 died of melanoma. 5µm slides were stained using Opal multiplexed IHC (mIHC) for DAPI, CD3, CD8, CD68, SOX10, HLA-DR and Ki67. Tumor areas were pre-selected by a dermatopathologist, visualized using Mantra (Perkin Elmer) and analyzed using inForm (Perkin Elmer) and Spotfire (TIBCO). Results: In all patients (n = 94), CTLs are farther from tumor (SOX10+) cells when they are proliferating (Ki67+) (p < 0.0001***), while they are closer to MΦ when they are activated (HLA-DR+) (p = 0.0002***). Next, we evaluated impact on prognosis using disease specific survival (DSS) as an outcome based on median value (n = 51). In this exploratory study no correction for multiple comparisons was made. We find that CTL density correlates with prolonged DSS in tumor (p = 0.0185*) but not in stroma (p = 0.1630 ns). Ratio of density of CD8/CD68+HLA-DR- correlates with DSS in both tumor (p = 0.027*) and stroma (p = 0.017*). Finally, distance from CTLs to HLA-DR- MΦ was significantly greater in non-recurrent melanomas as compared to recurrent ones (p = 0.0167*). Conclusions: HLA-DR expression on MΦ and Ki67 expression on tumor cells correlate with position of CTLs in TME in primary melanoma. CTL density is a favorable prognostic marker while HLA-DR non-expressing MΦ may favor tumor progression. Quantitative mIHC allows for accurate spatial analysis of immune subsets within the TME and the development of novel, more accurate and potentially clinically relevant biomarkers.
Hyperproliferative keratinocytic cutaneous adverse events and inflammatory palmoplantar erythrodysesthesia in melanoma patients treated with encorafenib compared to other BRAF inhibitors.
Authors: Goldinger Simone M. , Graf Natalie P , Galliker Nadja , Conrad Samuel , Dummer Reinhard 
Published: September 2018

9590 Background: BRAF inhibitor (BRAFi) an MEK inhibitor (MEKi) monotherapies have shown to cause more cutaneous adverse events (cuAEs) in monotherapy compared to combination therapy. Encorafenib in combination with binimetinib showed improved PFS in patients with BRAF mutant melanoma (14.9 months). Furthermore, encorafenib showed superiority over vemurafenib. Objective: The aim of this study was to investigate cuAEs of melanoma patients treated with encorafenib and/or binimetinib and compare them to other BRAFi and MEKi induced cuAEs reported in the literature and observed in our control population. Methods: Patients treated with encorafenib, binimetinib, and other BRAFi/MEKi within approved clinical trials at the University Hospital of Zurich were collected and analyzed. Clinical and histological assessments were performed. Results: In 111 patients treated with BRAFi and/or MEKi, 212 related or possibly related cuAEs were identified. The percentage of patients with at least one cuAE is shown in the table below. The most frequent cuAEs observed in patients treated with encorafenib where palmoplantar hyperkeratosis (PPH, 50%), palmoplantar erythrodysesthesia (PPD, 53.8%) and alopecia (42.3%), whereas acanthopapillomas (83%), maculopapular exanthemas (63.3%), PPH and PPD (each 50%) prevailed in patients treated with vemurafenib. The most frequent observed cuAE in patients with dabrafenib/trametinib combination therapy were maculopapular exanthemas (18.2%) and erythema-annulare-like eruptions (18.2%), with encorafenib/binimetinib combination therapy PPH (10.6%) respectivly. Conclusions: Encorafenib showed less hyperproliferative cuAEs as previous BRAFi. However, PPH and PPD seem to occur more often compared to the literature of other BRAFi. Both is supporting the argument that encorafenib is a second generation BRAFi with a longer dissociation time. [Table: see text]
Effect of incorporation of cisplatin to adjuvant chemotherapy for triple-negative breast cancer patients of unknown BRCA mutation status on survival.
Authors: Hung Chia-Yen , Su Ying-Wen , Hsieh Ruey Kuen , Lam Hung-Bun , Chang Yuan-Ching , Yang Po-Sheng 
Published: September 2018

e12009 Background: Recently, adding platinum to neoadjuvant chemotherapy (C/T) was associated with improved response rate in early Triple-negative breast cancer (TNBC). Whether incorporation of platinum to adjuvant C/T was associated clinical benefit has not been well investigated. Methods: Patients with resected TNBC who had available staging information and complete treatment at Mackay Memorial Hospital between 2004 and 2010 were enrolled for retrieving cllinical and pathologic information. Patients were monitored until death or Jan 2015. Statistical analysis was performed to determine the association of cancer-related overall survival (OS) and clinicopathological features. For stage I/II patients, 18 out of 115 received cisplatin-containing C/T. The mean OS for stage I/II patients with and without cisplatin-containing C/T was 6.05 years (standard error [SE]: 0.72 ) and 9.55 years (SE: 0.31), respectively ( P=0.07; log-rank test). For stage II/III patients, 20 out of 81 received cisplatin-containing C/T. The mean OS for stage II/III patients with and without cisplatin-containing C/T was 6.51 years (SE: 0.64) and 8.65 years (SE: 0.38), respectively ( P=0.56; log-rank test). In multivariate analysis for stage I-III patients, only age was significantly associated with OS (adjusted hazard ratio [HR]: 1.05; 95% confidence interval [CI]: 1.00-1.10). The adjusted HR for adding cisplatin to adjuvant C/T was 2.17 (95% CI: 0.729-6.44). Conclusions: In this small-numbered retrospective study, adding cisplatin to adjuvant C/T for TNBC with unknown BRCA mutation status did not have OS benefit. [Table: see text]
Correlation between Oncotype DX recurrence score and classical risk factors in early breast cancer.
Authors: Namuche Fernando , Ruiz Mendoza Rossana Esther , Flores Claudio J. , Aguilar Alfredo , Gomez Henry Leonidas 
Published: September 2018

e12011 Background: OncotypeDx(ODX) predicts the likelihood of estrogen receptor (ER) positive breast cancer (BC) recurrence and assesses the likely benefit from both hormonal therapy and chemotherapy. Many clinical scores that estimate the risk category of ODX are being tested. Ki67 is frequently incorporated into these assessments, although there is no standard cut-off for its use. Methods: We retrospectively reviewed the electronic medical files of 190 patients with early stage ER+ BC for whom ODX recurrence score (RS) was available from 2014 to 2016. Our objective was to find out the degree to which classical clinicopathological variables -as defined by St. Gallen(SG) 2015- could predict ODX risk category, also to determine an optimal Ki67 cut-off in order to establish an accurate classification. Chi square test was used. Results: Mean age at diagnosis was 59 years (28-89). Mean tumor diameter was 15mm, 84.2% were intermediate grade. Mean expression of ER, PR and Ki67 were 87%, 53% and 22%, respectively. According to ODX 62.1% patients were low risk, 30.5% intermediate risk and 7.4% high risk. An overall concordance of 46.8% (73/190) was found between SG 2015 and the risk category of ODX (75.7% for low, 33.3% for intermediate and 23.9% for high RS). When changing SG Ki67 cutoffs to ≤20% (for low Ki67) and ≥30% (for high Ki67), an overall concordance of 56.3% (107/190) was found (69.6% for low, 47.3% for intermediate and 23.9% for high RS, with p=0.00) (Table 1). Conclusions: In best-case scenario, SG classical clinicopathological variables correctly classified 56.3% of patients of our series. Despite being a specialized center, the utility of classical clinicopathological variables for predicting ODX risk category is limited. [Table: see text]
Biology and prognosis of HER2-negative breast cancer with low-ER and PgR-expressions.
Authors: Nishimura Reiki , Osako Tomofumi , Nishiyama Yasuyuki , Okumura Yasuhiro , Fujisue Mamiko , Toyozumi Yasuo , Arima Nobuyuki 
Published: September 2018

e12020 Background: Expression of the estrogen (ER) and progesterone receptor (PgR) is still clinically important in predicting prognosis and determining therapeutic strategies in breast cancer. According to the ASCO and CAP guidelines tumors with ≥1% positively staining cells should be considered ER/PgR positive. The clinical significance of low-ER/PgR-staining (1-9%) tumors were analyzed to investigate the biology and prognosis. Methods: This study examined 3193 consecutive HER2 negative invasive breast cancer cases. Clinicopathological characteristics and prognosis of hormone receptor (HR)-negative (<1%), low-HR-staining (1-9%) tumors and positive (≥ 10%) tumors were compared. The median follow-up period was 75 months. Results: The following is the number of patients in each of the tumor categories: 466 ER cases (14.6%) and 775 PgR cases (24.2%) in the <1% group; 68 ER cases (2.1%) and 218 PgR cases (6.8%) in the 1-9% group; and 2559 ER cases and 2200 PgR cases in the ≥ 10% group. The age groups were; young (≤35 y), premenopausal (36-50 y), postmenopausal (51-65 y) and the elderly (≥66 y). The median ER positive cell rate was significantly lower in the young group. In contrast, the PgR expression was significantly higher in the premenopausal group and significantly lower in the postmenopausal group. Patients in the ≥10% group had significantly smaller tumors, lower Ki-67 values, a lower p53 overexpression and nuclear grade. The elderly group had better disease-free survival (DFS) and the young group had the lowest DFS. In addition, DFS by ER/PgR expression was more favorable in the ≥ 10% group than the other groups. Patients with 1-9% ER had significantly lower DFS than those in the ≥10% elderly group. Patients with 1-9% PgR had significantly lower DFS than those in all the ≥10% groups and significantly lower DFS than those in the <1% premenopausal group. Multivariate analysis for DFS revealed that PgR expression, lymph node metastasis and tumor size were significant prognostic factors. Conclusions: There was a clear difference in the PgR expression rate due to the menopausal status. Moreover, the 1-9% ER and PgR groups had biological features that were similar to ER/PgR-negative tumors.
Effect of obesity on the toxicity profile of patients with breast cancer treated with adjuvant chemotherapy.
Authors: Srinivasalu Vijay Kumar , George Annu Susan , Philip Arun , Kotne Sanketh , Bamroo Sahil , D.K. Vijaykumar , Pillai Ranjini , K Beena , Jose Wesley M , Pavithran Keechilat 
Published: September 2018

e12033 Background: There is increasing evidence that obesity is strongly associated with breast cancer (BC) and has a major impact on the patient tolerance, overall survival (OS) and progression free survival (PFS). Chemotherapy dosing as per body surface area (BSA) or the actual body weight is a major dilemma among the oncologists. Moreover, the side effects of chemotherapy in obese patients in an Indian population has not been described previously in literature. We intended to evaluate the major toxicity, OS and PFS in obese BC patients who received adjuvant chemotherapy (ADC) with Adriamycin/cyclophosphamide (AC) and paclitaxel (T). Methods: A retrospective analysis of 331 patients of BC who received 4 cycles of adjuvant AC + T from a single tertiary centre in South India between 2006-2014 were included . All patients were treated as per their BSA which were capped at 2. Body Mass Index (BMI) was divided into normal (18-22.99), Overweight (23-24.99) and Obese ( ≥25 as per Asian guidelines). The toxicity was scored as per NCI-CTCAE criteria. Results: Out of 331 patients, 213 were obese. On comparison of normal and over weight with obese patients, 65 (30.5%) in obese group had significant all grade neuropathy (p = 0.027), 65 (30.5%) had Grade 2 and 3 myelosuppression (p <0.001), 31 (14.5%) had all grade emesis (p = 0.031) and 28 (13.1%) had myalgia (0.001). The 5 year OS and PFS were 93.7% and 82.3% respectively in obese patients, higher than the patients with normal weight with a 5 year OS and PFS of 92.4 % and 76.9% , but was not statistically significant. Conclusions: Higher rates of severe toxicities were seen in obese BC patients who received ADC as per their BSA. The 5 year OS and PFS was better in obese BC patients, but was not statistically significant. [Table: see text]
Clinical outcomes in very early breast cancer (≤ 1cm): A national population based analysis.
Authors: Muzaffar Mahvish , Naqash Abdul Rafeh , Vohra Nasreen A. , Liles Darla K. , Wong Jan H. 
Published: September 2018

e12034 Background: The utilization of screening mammogram has resulted in increased diagnosis of very small breast cancers including T1a (≤5 mm), T1b ( > 0.5 but ≤1 cm). These small tumors have excellent prognosis with cancer-specific survival rates as high as 90% to 95%.This study evaluates outcomes in very early breast cancer in a national database. Methods: Patients with stage I breast cancer, tumor ≤ 1cm (T1aN0, T1bN0) diagnosed between 2006 and 2011 were selected from the SEER database. We excluded patients with missing biomarker information. Treatment outcome and prognostic factors for disease-specific survival (DSS) and overall survival (OS) were evaluated. Results: We identified 70,543 cases and included 54,796 patients with stageT1aN0M0 and T1bN0M0 in the final analysis.The mean age was 62.09 yrs(CI 95% 62.2-61.99),84% are white,7% black and 7% Other.89% were ER positive,11% ER negative and 3% had Her 2 positive tumors.71% of patients had T1b. ≤ 1cm breast cancer cases increased from 15% in 2006 to 18% in 2011.The 5-year disease specific survival (DSS) and overall survival (OS) for patients with stage T1aN0T1b N0 was 98.7% and 93.7%, respectively. Estrogen receptor(ER) positive tumors were associated with improved 5-yr DSS 99% vs 96% in ER negative (p < 0.0001) and OS in ER positive 94% vs 92%( p < 0.0001).Among white patients 5-yr DSS was 98.8% and OS was 93.7% while 5yr-DSS was 94%,OS 91.5% among black vs 5-yr DSS 99% and OS 96.3% in others( Asian or Pacific Islanders,AI), (p < 0.0001).Tumor subtype was not associated with significant difference in outcome but T1a tumor was associated with OS 94.5% vs 93.4% with T1b tumors(p < 0.0001) On cox model analysis factors which correlated with prolonged DSS and OS are race (p < 0.0001),older age (p < 0.0001), ER positivity (p < 0.0001) and tumor less than 5mm (p = 0.0006). Conclusions: Very early breast cancer is associated with excellent outcome but has some heterogeneity. Nonwhite/Non Black race was associated with better survival compared to white and black patients.ER positive tumors, older age were also associated with better outcome. This data while reassuring also brings into question of overtreatment of this disease subset.