bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunological evaluation of personalized peptide vaccination for metastatic breast cancer patients with triple-negative types.
Authors: Takahashi Ryuji , Toh Uhi , Iwakuma Nobutaka , Otsuka Hiroko , Shirouzu Kazuo , Matsueda Satoko , Shichijo Shigeki , Sasada Tetsuro , Itoh Kyogo 
Published: March 2020

e13046 Background: To develop cancer vaccine, we investigated immune responses of the patients (pts) with metastatic breast cancer (MBC) with triple negative (TN) types to personalized peptide vaccine (PPV). Methods: Thirty-four pts including 8 TN-MBC were enrolled a phase II study of PPV. A maximum of four HLA-class IA (A2, A3s, A24, A26)-matched peptides showing higher antigen-specific IgG responses were administered. Levels of IgG reactive to each of the 31 peptides in the pre- and post-treatment plasma at every 6 times of vaccination were measured using LUMNEX system. Peptide-specific CTL responses were examined by INF-g ELISPOT. Results: All 34 pts had significant pre-existing humoral immunity, whereas only 13 of 31 patients, including 3 of 6 TN cases, showed pre-existing cellular immunity. Thirty-one of 34 pts, including 6 TN cases, achieved more than one cycle (6 times) of vaccination. The augmentation of the IgG responses specific to at least one of the vaccinated peptides was observed in 18 of 31 pts, including 3 of 6 TN cases. CTL responses were augmented in 16 of 31 pts, including 5 of 6 TN cases. IgG responses were boosted to greater levels with 12th vaccination in all 31 pts tested including 6 TN cases. Best clinical responses of 6 TN cases were 1 CR, 0 PR, 5 SD, and 0 PD, while those of the other 25 cases were 1 CR, 1 PR, 17 SD, and 6 PD, respectively. Conclusions: There were no significant differences between TN cases and the other cases of MBC with regard to immunological humoral and/or cellular responses to PPV.
Efficacy endpoints (EEPs) in melanoma randomized controlled adjuvant trials (RCATs).
Authors: Monzon Jose Gerard , Petrella Teresa M. , Dancey Janet 
Published: March 2020

e13049 Background: Inconsistencies in RCAT EEPs definitions and reporting complicate the evaluation of EEPs as adequate surrogates for overall survival (OS) and the comparison of the EEPs between trials. We aimed to identify issues in reporting and defining of EEPs used in melanoma RCATs. Methods: To identify phase 3 melanoma RCATs published in English language journals from 1994- 2011, a Pubmed database search and systematic review of published meta-analyses were performed. RCAT characteristics and endpoint definitions were obtained. Original protocols were requested. Results: A total of 34 RCATs met the criteria for review. Interferon alone or in combination with another agent was the most commonly tested treatment. Node positive disease was included in 24 studies with 1 including resected metastatic disease. The eligibility criteria in regards to age, previous treatment, and performance status were not reported in 26%, 32%, and 53% of studies respectively. The baseline and follow-up radiological tests were not specified in 35% and 26% of studies respectively. Eight time-to-event (TTE) EEPs were identified, with most studies using more than one (See Table). The primary EEP was not specified 23% of the time. Clear definitions of TTE EEPs start and end time criteria were absent in 58% and 44% of studies, respectively. Conclusions: The inconsistencies in the reporting of EEPs in melanoma RCATs is due to a lack of standardization in their definition and measurement. Standardizing EEPs will reduce resource consumption and enhance the comparison of agents across studies in melanoma RCATs. [Table: see text]
Chalazion in multiple myeloma patients treated with bortezomib.
Authors: Mundia Mubasir , Mundia Abdul G. , Ali Mohammed Faisal , Ali Sana 
Published: March 2020

e13053 Background: Bortezomib, a proteosome inhibitor is an effective drug in treatment of multiple myeloma (MM). As single agent and in combination with other drugs it not only has antitumor effect but has also increased survival. There are many side effects associated with its use, including peripheral neuropathy. We report incidence of chalazion in myeloma patients treated with bortezomib. Methods: On clinical Chart review, there were 34 patients with stage 3 MM treated with bortezomib in 2010 and 2011 in a community oncology practice. There were 18 females, and 16 males. Their age ranging from 52-76 years with a median of 68years. There were 17 African American (AA) and 17 non African American (NAA) patients. 14 patients received single agent bortezomib, 10 received it in combination with dexamethasone, and other 10 in combination with lenalidomide, cyclophosphamide and steroids. All patients received bisphosphantes. Results: Four patients developed chalazion 11 to 22 months into treatment with bortezomib. Chalazion was relatively resistant to conventional therapy offered by the ophthalmologists, and persisted during therapy with bortezomib. 1 patient needed surgical intervention. 3 out of 4 patients were AA. There was no incidence of chalazion noted in solid tumor patients treated with chemotherapy that did not include bortezomib in the same time period. Conclusions: We believe, prolonged use of bortezomib is associated with 12-15% incidence of chalazion, which is relatively resistant to conventional therapy, and persist during use of bortezomib.
Prediction of the non-sentinel node metastasis in patients without clinically axillary lymph node metastasis, with implication of breast cancer subtypes.
Authors: Tominaga Shusei 
Published: March 2020

e13060 Background: The accuracy of the nomogram about non-sentinel lymph node metastasis (NSLNM ) in breast cancer patients is still controversial to avoid axillary dissection particularly sentinel lymph node biopsy was positive. The aim of this study was to evaluate the necessity of adding breast cancer subtypes to the NSLNM nomgram variables. Methods: Between 2009 and 2011, consecutive breast cancer patients without clinically axillary lymph node metastasis (n=140) who received sentinel lymph node biopsy at Higashiosaka General Hospital were studied retrospectively. Twenty-two patients were turned out that breast cancer already spread to the sentinel nodes and all of 22 patients received complete axillary lymph node dissection. Results: Twelve patients had only sentinel lymph node metastases(Group S), 10 patients had non-SLN metastases (Group A). Patient characteristics and average probability of spread to additional lymph node developed by Memorial Sloan-Kettering Cancer Center (MSKCC) Nomogram were almost the same results in both groups. However, subtypes of Group S consisted of 8 HER2 positive , 2 triple negative, and 2 luminal A cases, subtypes of Group A consisted of 4 luminal A and 6 luminal B cases. Conclusions: Our data suggested that luminal type breast cancer tends to spread to non-sentinel lymph node metastasis and adding HER2, Ki-67, and intrinsic biological subtypes may improve predictivity of MSKCC nomogram.
Expression of PRAME and MAGE-A3 in Asian and European patients with non-small cell lung cancer (NSCLC), bladder cancer, or hepatocellular carcinoma (HCC).
Authors: Therasse Patrick , Linder Albert , Thongprasert Sumitra , Yang Pan-Chyr , Lee Po-Huang , Tanwandee Tawesak , Kang Jin Hyoung , Lee Jungsin , Sittampalam Kesavan , Chotirosniramit Anon , Soo Ross A. , Van Poppel Hendrik , Lerut Evelyne , Joniau Steven , Coche Thierry , Gruselle Olivier , D'Agostino Diego , Myo Aung , Louahed Jamila 
Published: March 2020

e13061 Background: Antigen (Ag)-specific cancer immunotherapy is based on induction of immune responses (humoral and cell-mediated) specifically targeting Ags expressed by tumor cells. This may be achieved by delivering the Ag as a recombinant protein combined with potent immunostimulants. PRAME and MAGE-A3 are tumor Ags with distinct tumor expression patterns, both under investigation as targets for immunotherapy in NSCLC and malignant melanoma. For additional clinical development of these immunotherapies in other cancer types, expression of PRAME and MAGE-A3 in these cancers must be investigated taking into account patient ethnicity and tumor characteristics. Methods: 4 retrospective studies were performed, each including all tumor stages: NSCLC pts (in Asia and Europe); bladder cancer pts in Europe; HCC pts in Asia. Formalin-fixed paraffin embedded tumor tissues were tested for PRAME and MAGE-A3 expression by quantitative RT-PCR using an expression cut-off value for positivity. Exploratory analyses of possible associations with patient and tumor characteristics were done to identify factors that may impact Ag expression. Results: The overall Ag expression rates are shown in the table below. In NSCLC, both Ags were expressed less frequently in Asian than in European patients (the histological distribution was the same). NSCLC tumors more frequently expressed PRAME than MAGE-A3 while the reverse tendency was seen for bladder tumors and HCC. In the NSCLC studies, squamous cell carcinomas expressed both Ags more frequently than adenocarcinomas. No study found any association between tumor stage and Ag expression. Some 60% of the tumors express at least one of the Ags. Conclusions: The expression rates of PRAME and MAGE-A3 are sufficiently high to consider these Ags as targets for immunotherapy against NSCLC, bladder cancer and HCC. [Table: see text]
Pharmacokinetic advantage of hyperthermic intraoperative intraperitoneal cisplatin and oxaliplatin.
Authors: Lewin Sharyn Nan , Leinwand Joshua , Slavkovic Vesna , Webb Christopher , Weyker Paul , Raker Richard K , Graziano Joseph , Taub Robert N. 
Published: March 2020

e13066 Background: Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surface-spreading malignancies in order to maximize local drug concentrations while minimizing systemic effects. The pharmacokinetic advantage (PKA) of HIPEC is defined as the intraperitoneal to intravascular ratio of drug concentrations. We hypothesized that body surface area (BSA) and intravenous fluid (IVF) administration, by affecting intravascular volume, would correlate with PKA. Methods: On an IRB-approved study, we collected blood and peritoneal perfusate from 13 patients undergoing HIPEC with a set dose of 100 mg cisplatin (n=4) or a BSA-based dose of 250 mg/m2 oxaliplatin (n=9), and measured Pt concentrations by Inductively Coupled Plasma Mass Spectrophotometry. Areas under concentration-time curves from 0-60 minutes (AUC0-60) were calculated by Trapezoidal Rule. PKA was calculated by (AUC0-60[peritoneal fluid]/AUC0-60[plasma]). Linear regression and Wilcoxon rank-sum test were performed using SAS. Results: Models with both BSA and IVF as predictors of PKA fit better than BSA alone for cisplatin (p=.022 vs. p=.076) but not for oxaliplatin (p=.119 vs. p=.037). The BSA and IVF model was a better fit for peritoneal cisplatin (p=.003) than for plasma cisplatin (p=.146). The BSA-only model was a better fit for plasma oxaliplatin (p=.013) than for peritoneal oxaliplatin (p=.778). There was no statistically-significant difference between the median PKA of cisplatin vs. oxaliplatin (p=.706). Conclusions: Our results suggest that BSA is a better PKA predictor than the compound’s diffusion properties. When a set drug dose is used, rather than a BSA-based dose, IVF is also an important predictor. This is likely due to HIPEC’s limited duration, thus the drug does not reach equilibrium between the peritoneal and vascular compartments. When monitoring the pharmacokinetic parameters of HIPEC administration, factors influencing intravascular volume, including BSA and IVF, should be considered. Maintaining intravascular volume repletion is a key strategy for maximizing PKA, and thereby minimizing systemic side effects due to HIPEC.
Endocrine therapy in patients with metastatic breast cancers (MBC): Prognosis and measures of outcome.
Authors: Driol Pamela , Bonotto Marta , Fontanella Caterina , Gerratana Lorenzo , Valent Francesca , Russo Stefania , Andreetta Claudia , Minisini Alessandro , Sottile Roberta , Mansutti Mauro , Fasola Gianpiero , Puglisi Fabio 
Published: March 2020

e13070 Background: Endocrine manipulation is the cornerstone of therapy in hormone receptor (HR)-positive breast cancer. However, a significant percentage of patients who receive endocrine therapy (ET) as metastatic treatment experience de novo or acquired resistance. New clinical trials for HR-positive MBC should be tailored around immunophenotypical and clinical features. This study evaluates different potential prognostic factors in patients treated with ET for MBC. Methods: We analyzed retrospectively data from a series of 280 consecutive patients with HR-positive MBC diagnosed from January 2004 to February 2011 at University Hospital of Udine, Italy. Multivariate analysis was performed to establish the independent value of different disease and patients’ characteristics in influencing progression-free survival (PFS), overall survival (OS) and survival post-progression (SPP). Results: Median OS was 38.44 months (mo), median PFS at first-line ET was 10.05 mo. Median SPP was 22.74 mo, 15.18 mo, and 15.47 mo after first, second and third-line ET, respectively. Age >70 years and ECOG performance status >1 were independent prognostic factors for both shorter OS (HR 2.55, p = 0.019; HR 2.46, p = 0.025, respectively) and shorter SPP (HR 2.99, p = 0.003; HR 2.82, p = 0.011, respectively). Number of chemotherapy lines before first ET was an independent prognostic factor for both PFS (HR 1.45, p < 0.001) and OS (HR 1.62, p = 0.001). MIB-1 >14% was associated with shorter PFS (HR 1.98, p = 0.012); this finding underlines the poor prognosis of luminal B subtype in comparison with luminal A disease. Conclusions: Determinants of treatment decision-making in MBC include patients’ characteristics, prognostic factors, disease biology, and mechanisms of resistance. This study confirms the worse prognosis of luminal B subtype, also in presence of endocrine manipulation. Innovative therapeutic approaches are eagerly waited in order to overcome resistance to ET. This study also provides some insights for the choice of optimal endpoints in trials that enroll patients with HR-positive MBC. In particular, based on long SPP values, OS does not seem to be an appropriate endpoint in studies involving such patients’ population.
Phase I trial in advanced refractory solid tumors of the new drug first-in-class PDM08.
Authors: Barriuso Jorge , Moreno Victor , Coronado Monica , Galicia Ignacio , Soria Irene , de Castro Javier , Belda-Iniesta Cristobal , Martinez Marín Virginia , Custodio Ana , Redondo Andres , Lamarca Angela , Hindi Nadia , Subiza Jose Luis , Frias Jesus , Feliu Jaime , Carcas Antonio 
Published: March 2020

e13085 Background: PDM08 is a new active compound with antitumor activity in different cancer models. It is a synthetic derivative of the pyroglutamic acid. The lack of direct effect on tumour cells and antitumor activity in immunodeficient models indicates an immune response mediated mechanism. Toxicology and pharmacology preclinical studies showed a favourable safety profile, confirmed by a single-dose placebo controlled healthy volunteer phase I trial. Methods: A single institution open label phase I study was designed (NCT01380249). PDM08 was administered twice a week for four-week cycles. Initially an accelerate escalation phase was chosen with cohorts of 2 patients who after completing the safety period (2 weeks after last dose) had the possibility of escalate to the next dose level if no grade ≥ 2 toxicity and no progressive disease was observed. After 4 cohorts without meaningful toxicity, this design was amended to open new dose levels after a two-week period of treatment completed by the last patient of the cohort if no grade ≥ 2 toxicity was found. The trial was approved by the Ethics Committee and the Spanish Drug Agency. Extensive pharmacokinetic (PK) and pharmacodynamic (PD) data including serum cytokines, lymphoid subpopulations and immunoglobulins are collected. Preliminary efficacy was evaluated by PET-CT. Results: Since July 2011, 10 patients (pts) were recruited into 6 different dose levels (2pts were escalated) ranged from 0.560 mg to 14 mg. Pt characteristics were: female-male ratio 1:1. Median age: 67 (47-76). ECOG 0: 6 pts. 8 pts had colorectal cancer, 1 lung adenocarcinoma and 1 ovarian carcinoma. Median of previous treatments was 3 ranged 2 to 5. 3 pts presented G1 headache. No Dose Limiting Toxicities were found. Preliminary outcome data showed: best response stable disease for 4 patients, 2 of them being stable for 12 weeks. After 40 target lesions evaluated by PET-CT 6 (15%) showed a reduction in the maximum Standard Uptake Value (SUV) of 18-FDG. Conclusions: PDM08 is the first compound of a new class of drugs that can be dose-escalated safely in an accelerated manner and has promising activity. Last patient will be included in March 2012 so final data for toxicity, PK, PD and efficacy will be provided at the meeting.
Quality of life in patients with malignant ascites during catumaxomab treatment: Results from the CASIMAS trial.
Authors: Lordick Florian , Sehouli Jalid , Vergote Ignace B. , Rosenberg Per , Schneeweiss Andreas , Block Andreas , Salat Christoph , Scambia Giovanni , Berton-Rigaud Dominique , Siena Salvatore , Santoro Armando , Cervantes-Ruiperez Andres , Guastalla Jean Paul , Tournigand Christophe , Colombo Nicoletta , Dudnitchenko Alexander Serg , Bondar Vladimir , Westermann A.M. , Gonschior Ann-Katrin , Wimberger Pauline 
Published: March 2020

e13095^ Background: Malignant Ascites (MA) is associated with a poor prognosis and limited palliative treatment options. To demonstrate the value of a new treatment the assessment of quality of life (QoL) is of particular importance. Following the demonstration of catumaxomab’s potential to stabilize QoL and prolong the time to first deterioration of QoL, results from CASIMAS give evidence that the QoL of patients remains unaffected during catumaxomab treatment Methods: In a two-arm, open-label, multicentre phase II/III study 219 patients were randomized to catumaxomab plus premedication of 25 mg prednisolone (111 pts) or to catumaxomab alone (108 pts) QoL was measured using the EQ-5D visual analogue scale (EQ-VAS). The EQ-VAS reports the respondent’s self-rated health on a vertical scale where the endpoints are labelled “Best imaginable health state” (100) and “Worst imaginable health state” (0). This information is used as a quantitative measure of health outcome. Patients were asked to complete EQ-VAS during the treatment period (d 0, 3 and 10) and follow-up (d8, 28). Descriptive analyses were performed according to EQ-5D User Guide (Version 4.0). Additionally ascites related symptoms were measured with a disease specific FACIT patient questionnaire. Results: For the pooled population (catumaxomab plus prednisolone and catumaxomab alone) longitudinal analysis of the EQ-VAS showed no relevant changes in mean score during the treatment period of catumaxomab (d0: 51.5; d3: 50.9; d10: 51.0) and compared to screening (52.7). An increase in mean values was observed in the follow-up period (d8: 53.9, d28: 57.1). Descriptive comparison of both treatment groups revealed no major differences in QoL and ascites related symptoms during the treatment and follow-up period, indicating that prednisolone has no impact on patient`s self-rated health. Conclusions: This analysis shows that QoL as measured by EQ-VAS remains unaltered during the treatment with catumaxomab and improves after the treatment period. The improvement is plausible due to the prolonged-puncture-free survival and is consistent with previous observations of QoL changes during and after intraperitoneal treatment with catumaxomab.
Catumaxomab with and without prednisolone in patients with malignant ascites due to epithelial cancer: Results from the phase IIIb CASIMAS study.
Authors: Sehouli Jalid , Wimberger Pauline , Vergote Ignace B. , Rosenberg Per , Schneeweiss Andreas , Bokemeyer Carsten , Salat Christoph , Scambia Giovanni , Berton-Rigaud Dominique , Siena Salvatore , Santoro Armando , Cervantes-Ruiperez Andres , Guastalla Jean Paul , Tournigand Christophe , Colombo Nicoletta , Dudnitchenko Alexander Serg , Bondar Vladimir , Westermann A.M. , Lordick Florian 
Published: March 2020

e13097^ Background: The primary objective of this study was to compare catumaxomab with prednisolone (CP) to catumaxomab without prednisolone (C) as 3-hour intraperitoneal (i.p.) infusion by demonstrating superiority for safety and non-inferiority for efficacy of the CP arm. Methods: 219 patients were randomized to catumaxomab plus premedication of 25 mg prednisolone (111 pts) or to catumaxomab alone (108 pts). The primary endpoint was the composite safety score (CSS) summarizing the worst CTCAE grades for the main TEAEs (pyrexia, nausea, vomiting, and abdominal pain). A potential impact of prednisolone on efficacy was assessed by the co-primary endpoint puncture-free survival (PuFS). Further parameters included overall survival (OS) and time to next therapeutic puncture (TTPu). Results: The superiority of CP for safety was not proven as the mean CSS was comparable in the two groups (CP: 4.1; C: 3.8 for; p= 0.383). The median PuFS was slightly lower in CP (30 days) compared to C (37 days). However the hazard ratio (HR) for PuFS (HR: 1.130, p=0.402) as well as the 75% quartiles (CP: 155 days, C: 92 days) were in favour of CP compared to C. The median TTPu was similar in both groups (CP: 78 days; C: 102 days, p= 0.599). The majority of patients (123 pts) had no therapeutic paracentesis prior to death (CP: 54.8%; C; 61.7%, p=0.297). Median OS was longer for CP (CP: 124 days; C: 86 days, p= 0.186) without statistical significance. Conclusions: The CASIMAS results are in concordance with the data of the pivotal study and thus confirm the robustness of the treatment effect of catumaxomab in malignant ascites. The administration of 25mg prednisolone as premedication prior to catumaxomab infusion did not change the safety profile and did not negatively impact the efficacy of catumaxomab. The composite safety score after 3-hour infusion time was comparable to that seen in the pivotal study using 6 hours.