bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and complications associated with off-label use of lenalidomide in older patients with myelodysplastic syndromes (MDS).
Authors: Brunner Andrew Mark , Weng Shicheng , Cronin Angel M. , Fathi Amir Tahmasb , Stone Richard M. , Graubert Timothy A. , Steensma David P. , Abel Gregory A. 
Published: September 2018

7054 Background: Lenalidomide (LEN) is approved for patients with lower-risk MDS with del5q who are transfusion-dependent (TD). We aimed to assess the prevalence and complications associated with LEN use in non-TD older patients with MDS. Methods: Using the SEER-Medicare database we identified Medicare enrollees diagnosed with MDS from 2007-2011. Medicare part D claims were analyzed for evidence of LEN use. CPT, HCPCS, and ICD-9 codes were used to characterize TD MDS (claims for ≥ 2 RBC transfusions within 8 weeks prior to LEN), complications, and baseline risk per SEER-Medicare MDS Risk Score (SMMRS; Uno, Leuk Res 2014). Incident complications during LEN were noted if there were no prior claims for the same within a 1-yr look-back window. Results: Among 469 patients initiating LEN (median age 78 years), 77% received it first-line, and 23% after a hypomethylating agent. Among all, 19% had del5q, 37% had non-del5q MDS, and 44% no histology specified (MDS NOS). SMMRS risk was evenly distributed between low (36%), intermediate (30%), and high (34%). Only 42% of patients were TD at the time of first LEN prescription, and 26% had not been transfused within six months prior to LEN. Non-TD patients receiving LEN were more likely to have lower-risk disease (p = .004), and less likely to have pre-treatment thrombocytopenia (p = .005) or neutropenia (p = .003); they did not differ significantly in age (p = .85), documentation of del5q (p = .51), comorbidity (p = .65) or treatment center volume (p = .80). Median days on LEN for the non-TD was 121. Incident complications post-LEN among the non-TD are shown. Conclusions:These data suggest there is widespread off-label use of LEN in older patients with MDS, as many receive the drug who are not TD. Moreover, off-label exposure to LEN in these patients is associated with a sizable risk of incident complications, which is difficult to justify given they are already living free of transfusion dependence. [Table: see text]
Identification of effective therapy in Langerhans cell histiocytosis in the adult population.
Authors: Ma Jennifer , Laird James , Chau Karen , Chelius Monica , Bell Andrew C. , Lok Benjamin H. , Yahalom Joachim 
Published: September 2018

7065 Background: Langerhans cell histiocytosis (LCH) is a rare disorder of histiocytic proliferation most commonly observed in children. LCH in adults is less characterized and a standard of care has not been established. Here we review clinical outcomes of adult LCH patients (pts) treated with various therapies at a large referral center. Methods: We identified 108 pts over 18 years of age with histologically confirmed LCH presenting to our center between 1990-2015. Clinical and treatment characteristics were examined and classified by single or multi-system involvement (SSI or MSI, respectively) and risk-organ involvement (ROI; liver, spleen, hematopoietic system and CNS). Overall survival (OS) and freedom from first progression (FFFP) were calculated by the Kaplan-Meier method. Univariate analysis was performed with the Cox proportional hazards model. Results: Median age at diagnosis was 44 years (range 18-89) with a median follow-up of 3.9 years (0.1-9.1). Median OS was 16.1 years and FFFP was 5.6 years, with 94 (87%) pts alive at last follow-up. Eighty-three (77%) had SSI and 13 (12%) had ROI. The most common sites of disease were bone (52 pts; 48%), lung (28; 26%), and skin (24; 22%). Only 11 pts (9%) experienced progression of disease (POD) after first treatment. Twenty-four (22%) received radiotherapy, 42 (39%) underwent excision, and 26 (24%) received systemic therapy at any point during treatment. The most common systemic agents were vinblastine, 6-mercaptopurine (6-MP), methotrexate (MTX), and cladribine. Eight received combination vinblastine, 6-MP, and MTX (VMM), 4 of which had MSI. Median progression-free survival (PFS) of VMM pts was 6 months, compared with 2.8 for all other systemic agents (p = 0.1). For OS, lack of ROI was the only significant variable upon univariate analysis (HR .22, 95%CI 0.06-0.75, p = 0.016). No variables were significant for PFS. Conclusions: Effective therapy for adult LCH has not been clearly identified. In our cohort of both low and high risk patients, the low POD rate observed is encouraging. VMM, a regimen previously studied in pediatric pts, is also effective in adults and may be considered the combination of choice for treatment of adult LCH. Further prospective study is warranted.
Trabectedin (T) as second line treatment option for patients with epithelioid malignant pleural mesothelioma (MPM) in progression following pemetrexed/platin-derivates chemotherapy: ATREUS trial.
Authors: Cortinovis Diego Luigi , Hollander Lital Hannah , Carlucci Luciano , Grosso Federica , Ceresoli Giovanni Luca , Pacchetti Ilaria , Zucali Paolo Andrea , D'Incalci Maurizio , Tiseo Marcello , Legramandi Lorenzo , Canova Stefania , Ugo Francesca , Abbate Maria Ida , Taverna Giacomo , Cogliati Viola , Bidoli Paolo 
Published: September 2018

8513 Background: Systemic chemotherapy in MPM is inevitably followed by relapse, and response rates to second line treatment are limited. T is an antineoplastic agent targeting both the malignant cells and the tumor microenvironment with demonstrated activity against a range of tumors. We aimed to study the activity and safety of T in advanced MPM. Methods: ATREUS, an Italian multicenter single arm phase II trial, assessed the activity T in MPM evaluating the proportion of patients responding to treatment and achieving progression free survival for 12 weeks (PFS12w). Pre-treated epithelioid and naive or pre-treated biphasic/sarcomatoid pts were treated until progression or unacceptable toxicity. Initial dose was 1.3 mg/m2, over 3 hours every 21 days, later reduced to 1.1 mg/m2to improve tolerability. In the epithelioid cohort, sample size was based on a Simon's Optimal Two-Stage Design. The study was set to reject, at an alpha error of 10% the hypothesis that PFS12w was ≤25% and to demonstrate, with a power of 85% the hypothesis that PFS12w was ≥40%. At least 20 out of 62 pts with assessed disease, no major protocol violations, either receiving ≥12 weeks of treatment or interrupting before for progression or death (per protocol – PP analysis) were to reach PFS12w in order to consider T effective. Results: 71 pts were enrolled and evaluable. Average age was 65.8 ± 8.75 years. 71.8% were male and 82.5% presented stage III or IV disease. 42.4% (25/59) of pts included in the PP analysis obtained PFS12w (95% CI: 29.6% - 55.9%). In a second, more conservative analysis, including pts withdrawn prematurely for toxicity or intercurrent illness as failures, PFS12w rate reached 38.5% (25/65 pts). The most frequent grade ≥3 treatment-related toxicities werehepatic toxicity (60.5%), non-febrile neutropenia (21.1%), and fatigue (6.6%). Five pts (7%) interrupted treatment for toxicities (2 liver, 1 multi-organ failure, 1 thrombocytopenia, 1 T intolerance). Conclusions: In pts with advanced epithelioid MPM, second line treatment with T showed an elevated rate of disease stabilization. Safety data is promising but require further evaluation. Clinical trial information: NCT02194231.
Humanistic burden of disease in earlier stage metastatic (stage IIIb/c-IVM1a) versus late stage metastatic (IVM1b/c) melanoma patients in a real-world setting in the U.S.
Authors: Buchanan Jacqueline , Murugappan Swaminathan , Moon Rebecca , Roughley Adam , Rider Alex 
Published: September 2018

9561 Background: To assess melanoma specific health-related quality of life (HRQoL) and health states in patients with earlier stage metastatic (IIIb/c-IVM1a) versus late stage metastatic (IVM1b/c) melanoma. Methods: Data were collected from the Adelphi Real World Advanced Melanoma Disease-Specific Programme, a cross-sectional survey of 112 physicians and their patients (N = 666). Data were collected between March and July 2016 in the US. A subset of 183 patients completed the Functional Assessment of Cancer Therapy Melanoma (FACT-M) and EuroQol-5D (EQ-5D) one time. Patients were classified by stage of melanoma at time of consultation. Descriptive analyses of HRQoL scores between earlier and late stage metastatic melanoma were assessed using Mann-Whitney U tests. Results: The mean age of the earlier stage and late stage metastatic patients was 62 and 64 respectively. More earlier stage metastatic patients had an ECOG status of 0 or 1 versus late stage metastatic patients (85%, 75% respectively). A total of 31% of late stage metastatic patients required caregiver support and had a median time since primary diagnosis of 5.0 months whereas earlier stage metastatic patients reported 14% and 5.2 months respectively. Patients with earlier stage metastatic melanoma had better mean EQ-5D index scores versus late stage metastatic melanoma patients (0.81 (n = 84), 0.76 (n = 93); p = 0.0103). Higher scores indicating better HRQoL were observed between earlier stage metastatic versus late stage metastatic melanoma patients for the FACT-M (120.7 (n = 81), 107.4 (n = 91); p = 0.0017) and subscales (except Social Well Being). Clinically meaningful differences between groups using published minimal important differences (MIDs) were observed in in 6/7 FACT-M subscales and EQ-5D VAS. Conclusions: Differences in HRQoL and health states were observed between earlier stage metastatic and late stage metastatic melanoma populations, highlighting the detrimental effect of developing metastatic disease. These results suggest that treatments that delay progression of the disease are important to conserve patients HRQoL
Determinants of adjuvant chemotherapy use in small luminal-like breast cancer.
Authors: Bonotto Marta , Gerratana Lorenzo , Bettini Alessandro , Cinausero Marika , Basile Debora , Pelizzari Giacomo , Vitale Maria Grazia , Bozza Claudia , Lisanti Camilla , Fanotto Valentina , Bartoletti Michele , Andreetta Claudia , Russo Stefania , Poletto Elena , Iacono Donatella , Mansutti Mauro , Minisini Alessandro Marco , Fasola Gianpiero , Puglisi Fabio 
Published: September 2018

e12010 Background: The use of adjuvant chemotherapy (CT) in small luminal-like breast cancer (BC) is still heavily debated. International guidelines identify endocrine therapy as the backbone of adjuvant treatment for these patients (pts), while the addition of CT should be limited to high risk cases. The aim of this study was to evaluate the association between patient- or disease-related factors with the prescription of adjuvant CT. Methods: This retrospective study reviewed data from 559 consecutive pts with pT1 ( < 2 cm) luminal-like BC treated between 2004 and 2015 at the Department of Oncology of Udine (Italy). No restrictions were applied regarding lymph node status. The cut-off point of 1% was used to define ER and/or PgR positivity. Factors influencing the prescription of CT were investigated through uni- and multivariate logistic regression with odds ratio (OR) calculation. Prognosis was explored through Cox regression. Results: About thirty percent (173/559) of pts received adjuvant CT. By multivariate analysis, lymph node involvement was highly associated with CT prescription (OR 16.94, 95% CI 7.86-36.50, P < 0.001 for pN1; OR 3.92, 95% CI 1.45-10.58, P = 0.007 for pNmi). Tumor size drove towards the use of CT among pts with pT1c tumors (OR 12.87, 95% CI 1.49-110.88, P = 0.020) but not in pts with pT1b BC (OR 2.38, 95% CI 0.26-21.38, P = 0.437). In addition, a higher CT use was observed in pts with luminal B-like disease (OR 3.79, 95% CI 2.16-6.65, P < 0.001) or in presence of a Ki67 > 14% (OR 1.05, 95% CI 1.03-1.07, P < 0.001). On the contrary, pts with age > 60 years had a very low chance of receiving adjuvant CT (OR 0.09, 95% CI 0.04-0.20, P < 0.001). Notably, the use of CT was not associated with Disease Free Survival or Overall Survival (HR 1.3, 95% CI 0.77-2.17, P = 0.320; HR 1.05, 95% CI 0.56-2, P = 0.866; respectively). Conclusions: Nodal status, tumor size, disease sub-type, Ki67 expression and age are determinants of adjuvant CT prescription in pts with small luminal-like BC. Prospective studies are needed to identify which pts could safely avoid CT without influencing prognosis.
Effect of trastuzumab emtansine (T-DM1) on autologous platelet kinetics.
Authors: Gadi Vijyakrishna , Corson Jill , Cundy Arianne , Bailey Shawn , Pellham Esther , Christoffel Todd , Gettinger Irena , Barroso Jeffrey , Slichter Sherrill 
Published: September 2018

e12521 Background: T-DM1 treatment results in Grade 3-4 thrombocytopenia in 8%-13% (1.4% with clinically significant bleeding). Prior in vitro studies reported T-DM1 inhibition of megakaryocyte maturation as the cause of decreased platelet production. The current study was initiated to evaluate the cause of thrombocytopenia in patients. Methods: Patients with HER2-positive metastatic breast cancer (N = 10) were enrolled in this Phase 1 study. 111In radiolabeled autologous platelet recoveries and survivals as well as serial platelet counts, bleeding time assays, platelet aggregation responses to epinephrine, adenosine diphosphate, collagen, arachidonic acid, ristocetin, and thromboxane were performed at baseline and during two consecutive cycles (C) of the drug (3.6mg/kg IV q3weeks). Results: Platelet nadir occurred on days (D) 7, 8, or 9 post-T-DM1 in C1 and at D5-6 in C2. Average nadir counts (% baseline) in C1 and C2 were 116,000/µl (52 ±22%) and 117,000/µl (48 ±31%), respectively, with return to baseline by D15 in both cycles. Autologous 111In-labeled platelet recoveries averaged 64 ±10%, 65 ±12%, and 65 ±12% at baseline, C1 and C2, respectively. Baseline platelet survival averaged 8.8 (±1.1) days but progressively shortened to 5.4 (±1.6) days during C1 and 4.6 (±1.0) days during C2 (p < 0.001 compared to baseline for both cycles). Bleeding times were appropriate for the corresponding platelet count throughout both cycles. Aggregation responses to all agonists decreased during the study, more in C2 than in C1. Conclusions: Following T-DM1 administration, platelet kinetic measurements demonstrated statistically significant progressive decreases in platelet survivals from normal baseline values (decreased survivals were observed in all patients treated on study). In distinction to published in vitro studies, these unexpected results indicate a direct toxic effect of T-DM1 on patients’ autologous circulating platelets. In addition, autologous aggregation responses were decreased, suggesting drug-induced platelet dysfunction. Clinical trial information: NCT01816035.
Targeted combination therapy with fulvestrant (FUL) for second-line (2L) treatment of hormone receptor-positive (HR+) advanced breast cancer (ABC).
Authors: Mayer Ingrid A. , O'Regan Ruth , Kornblum Noah Saul , Blackwell Kimberly L. 
Published: September 2018

e12527 Background: FUL is the recommended 2L treatment for patients whose HR+ ABC progressed after aromatase inhibitor (AI) therapy. In first line ABC adding targeted therapy, eg. cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) palbociclib or ribociclib, or mammalian target of rapamycin inhibitor (mTORi) everolimus (EVE), to endocrine therapy (ET) has shown superior efficacy vs ET alone. The use of similar strategies to delay disease progression on ET in the 2L setting is an area of active research. Methods: PubMed and ClinicalTrials.gov were searched for trials investigating FUL + targeted therapies in 2L HR+ ABC. Search terms: (advanced OR metastatic) AND (breast cancer) AND (FUL OR faslodex) AND (2L OR relapse OR refractory OR resistant OR progression). Efficacy, adverse events (AEs) and quality of life were assessed. Results: 28 studies of FUL + targeted therapies in 2L ABC were found. Key randomized trials include 8 studies exploring FUL + CDK4/6i: palbociclib, ribociclib or abemaciclib. Palbociclib + FUL significantly improved progression-free survival (PFS) vs FUL in 2L HR+ ABC (p < 0.0001; PALOMA-3), AEs were manageable. Assessment of FUL + ribociclib (MONALEESA-3) or FUL + abemaciclib (MONARCH-2) in 2L HR+ ABC is ongoing. Ten studies are evaluating FUL + phosphatidylinositol 3-kinase (PI3K)/AKT/mTORi in 2L HR+ ABC. FUL + EVE significantly prolonged PFS vs FUL (p = 0.02; PrECOG 0102). Two trials evaluated buparlisib (pan-PI3K inhibitor [PI3Ki]) + FUL in HR+ ABC post-AI (BELLE-2) and post-mTORi (BELLE-3). In both trials, buparlisib + FUL improved PFS vs FUL in patients with PIK3CA-mutated tumors, FUL alone led to a poor response in this subgroup. However, pictilisib (pan-PI3Ki) + FUL did not improve PFS vs FUL even in the PIK3CA-mutated subgroup (FERGI). Ongoing phase 3 trials are exploring FUL + alpelisib (α-specific PI3Ki; SOLAR-1) or FUL + taselisib (β-sparing PI3Ki; SANDPIPER) in PIK3CA-mutant HR+ ABC. Pts who have progressed on AI, CDK4/6i or (neo)adjuvant chemotherapy are eligible for these studies. Data on FUL + other targeted therapies will also be discussed. Conclusions: Addition of targeted therapy to FUL demonstrates promising efficacy beyond first line.
Surgical ovarian ablation for hormone receptor positive primary breast cancer in premenopausal women.
Authors: Oseledchyk Anton , Gemignani Mary , Dickler Maura N. , Goldfarb Shari Beth , Iasonos Alexia , Zhou Qin , Carter Jeanne , Barakat Richard R. , Abu-Rustum Nadeem , Zivanovic Oliver 
Published: September 2018

e12536 Background: Ovarian ablation is increasingly used to complement endocrine therapy in select premenopausal women with hormone-receptor positive (HR+) breast cancer (BC). It can be achieved by either medical ovarian suppression (OS) or therapeutic bilateral salpingo-oophorectomy (BSO). We sought to investigate trends of therapeutic BSO in premenopausal patients at our institution. Methods: Premenopausal women with HR+ primary BC diagnosed from 2010-2014 were identified in our prospectively maintained BC database. Patients with confirmed BRCA1/2 mutations were excluded. Distribution of patient and disease characteristics between treatment groups were assessed using univariate logistic regression analyses. Surgical details and complications were extracted from our surgical database. Results: We identified 2,854 eligible patients; 2,113 (74%) received endocrine therapy without ovarian ablation, 246 (9%) received endocrine therapy plus medical OS, 180 (6%) underwent additional BSO, and 315 (11%) did not receive endocrine therapy at the time of analysis. Independent predictors for undergoing ovarian ablation were younger age (OR 0.98; 95%CI, 0.96-0.99; p < 0.001), higher grade (grade 3 vs 1: OR 3.17; 95%CI, 1.70-5.90; grade 2 vs 1: OR 3.13; 95%CI, 1.64-5.95; p < 0.001), lymph node involvement (OR 1.46; 95%CI, 1.19-1.80; p < 0.001), and higher AJCC stage as well as de novo metastatic BC (II vs I: OR = 1.35; 95%CI, 1.03-1.76; III vs I: OR 2.57; 95%CI, 1.86-3.55; IV vs I: OR 19.69; 95%CI, 12.76-30.39; p < 0.001). Among patients who underwent ovarian ablation, patients of younger age (1.04; 95%CI, 1.01-1.07; p = 0.009) and with metastatic BC (stage IV vs I: OR 0.36; 95%CI, 0.20-0.68; p = 0.007) were less likely to undergo BSO than OS. In 180 patients undergoing BSO, five adverse events were noted: two grade 1, two grade 2, and one grade 3 complication. Conclusions: Premenopausal women with HR+ BC with high-risk features or metastatic disease were more likely to undergo ovarian ablation at our institution. Surgical ovarian ablation is a safe alternative, with low complication rates. Understanding patient preferences, side effects, and quality of life implications will help guide personalized treatment decisions.
Incidence patterns and survival of gynecological sarcoma in Germany: Analysis of population-based cancer registry data on 2106 women, 2009-2013.
Authors: Pietzner Klaus , Buttmann Nina , Sehouli Jalid , Kraywinkel Klaus 
Published: September 2018

e13058 Background: Sarcoma of the female genital tract are rare tumors. They are described to be associated with a poor prognosis, when compared to gynecogical carcinoma. Aim of this study was to report incidence patterns and survival rates for gynecological sarcoma in Germany. Methods: Clinical data and survival rates for patients with gynecological sarcoma diagnosed in Germany between 2009 and 2013 were extracted from the German national centre for population-based cancer registry data. Incidence patterns and 5-year-relative survival rates were calculated. Results: A total of 2,106 gynecological sarcoma (GS) were eligible for analysis. The uterus was the most common site with 87.2% of all cases. The annual age-standardized incidence rate was 7.7 per 1 million women for all gynecological sarcoma. The median age at diagnosis was 59 years. The prognosis ranged according to site and subtype from a poor 5-year-relative survival of 47.6% (uterine leiomyosarcoma) to a very good 5-year-relative survival of 97.2% (endometrial stromal sarcoma). Conclusions: Despite the rareness of gynecological sarcoma, the size of the dataset allows a differentiation of subtypes according to morphology and site of origin. Clinically relevant differences in incidence and prognosis between subgroups were observed.
Triple negative breast cancer in a South African urban breast care centre.
Authors: Prodehl Leanne , Benn Carol 
Published: September 2018

e13067 Background: Triple negative breast cancer (TNBC) is associated with advanced stage at presentation, aggressive tumour biology and poor outcomes. There is no published data for South Africa. Methods: A retrospective file review of TNBC cases at the Milpark Breast Care Unit in Johannesburg, South Africa, data were collected on presentation, treatment and outcomes. A prospective file review and telephonic interview were done for further follow up. Results: There were 196 patients with TNBC identified out of 1407 patients (13.9%), 135 patients were analysed. Stage at presentation was IIa and IIb in approximately half (46.7%) of the patients and IIIa, IIIb and IV in a third (31.8%). Patients presented with large tumours -71.8% were T2 to T4; and lymph node positive disease (55.6%). The majority of patients had high-grade, poorly differentiated tumours. The challenges when treating TNBC were reflected in the use of multimodality therapy; 92.2% of patients had chemotherapy, as neoadjuvant (59.3%), adjuvant or both. There were 93 (68.9%) patients treated with adjuvant radiation therapy. If neoadjuvant chemotherapy was given 91.2% had a response. Recurrences occurred in 33 patients, with a 5-year disease free survival of 72.5%, and preponderance to visceral metastases (45.2%). Recurrences occurred early, the median was 23.1 months and all had occurred within eight years. Younger patients (HR 1.58), tumour size and lymph node positivity (HR 4.42) were associated with increased risk of recurrence, but only lymph node positivity was significant (HR 4.42). Complete pathological response to neoadjuvant chemotherapy was associated with fewer recurrences if no tumour was found in either the breast or the lymph nodes (HR 0.33). The 5-year overall survival was 76.4%. There was no significant difference in survival for age, node status, nuclear grade, or complete pathological response, only tumour size at presentation was significantly associated. Conclusions: The prevalence of triple negative breast cancer in a South African breast care unit was similar to some European studies but less than studies in West and East Africa. Patients presented at an advanced stage and had poorer outcomes than luminal breast cancers.