bluuebunny/crossref_metadata_2025_split huggingface dataset:
A study of tolerance to treatment among the most frequent cancer in the elderly
Authors: Pilnik N. G. , Werbin R. , Dirienzo J. 
Published: March 2020

18609 Background: Besides, aging may influence pharmacological aspects due to functional reserve deterioration and comorbidities, affecting tolerance to treatment and increasing the likelihood of complications. Methods: 166 cancer pts (56 lung, 64 breast, and 46 colon), mean age 72 yrs, treated with Ch/Rt were studied. Lung cancer pts had PS 0:1 (2%); PS 1:17 (30%); and PS2:38 (68%). Breast cancer pts had PS 0:6 (9%); PS 1:25 (39%); PS 2:33 (52%). Colon cancer pts had PS 0:6 (13%); PS 1:17 (37%); PS 2:23 (50%). Comorbidities were hypertension, diabetes, arrhythmia, EPOC, coronary and gastrointestinal disease. All of the pts had adequate cardiac, hepatic, renal and bone marrow functions. Allergy, cardiovascular, gastrointestinal, hepatic, neurological, haematological and renal toxicities, and infection were evaluated following the WHO criteria. Toxicities were studied according to age and comorbidities, and correlated with the use of other medicines. QoL was studied through the improvement of symptoms and PS evolution. The Chi Square test was used for statistical analyses. Results: The prevalence of common toxicities in the lung cancer pts were anemia, 39 pts (70%), infection, 37 pts (66%), leukopenia 33 pts (59%), gastrointestinal 28 pts (50%). The most common toxicities in breast cancer, were leukopenia 43 pts (67%), gastrointestinal 37 pts (58%), infection 36 pts (56%), and anemia 32 pts (50%), while in colon cancer pts the toxicities found were gastrointestinal 38 pts (83%), anemia 33 pts (72%), leukopenia 32 pts (70%), and infection 25 pts (54%). There was no correlation between age and the most frequent toxicities. Grade 2 was the most common level of toxicity reached in all types of cancer studied. There was improvement in QoL when symptoms evolution and PS were evaluated independently of cancer type, 81% (134 pts) for symptoms (p < 0.0001), and 72% (120 pts) for PS (p < 0.0001) respectively. There was no association between age and toxicity grade, irrespective of toxicity type, age and comorbidities. Conclusions: Older pts in good general condition and with controlled morbidities may receive Ch/Rt if this treatment modality results in improvement of their QoL.-Low toxicities occurred in most of these pts, probably due to the fact that pts were adequately selected. No significant financial relationships to disclose.
Death predicictive factor in terminal cancer patients
Authors: Koh S. , Lee K. , Hong Y. , Kang J. , Woo I. , Lee M. , Chang S. 
Published: March 2020

18627 Background: One of the most important role of a end-of-life care is to control physical symptoms of patients and help them to face comfortable end. In terminally ill cancer patients, accurate prediction of survival is necessary for clinical and ethical reasons, especially in helping to avoid harm, discomfort and inappropriate therapies and in planning specific care strategies. The aim of the study was to investigate prognostic factor of death for the patients with terminal cancer. Methods: We enrolled 121 patients with the terminal cancer of Kangnam St. Mary’s Hospital from September 2004 until their death. We observed symptoms shown in dying patients and assess 17 common symptoms shown in terminally ill cancer patients, performance status, pain and analgesic use. The common symptoms were measured in a score of 0-none, 1-mild, 2-moderate, 3-severe or 4-severe by objective criteria. Results: Mean period from enrollment to death was 34.7days. The most important prognostic factor is performance status (KPS), average KPS at enrollment is 52.2% and at last 48hours is 29.8%. Physical symptoms that have significant prognostic importance are weakness, anorexia, dry mouth, dysphagia, dyspnea. VAS and analgesic use dose not impact on the prognosis. But cognitive impairment and delirium are the reliable prognostic factor. Especially weakness, dry mouth, poor oral intake, drowsiness, edema, dyspnea, ascites, icterua gradually worsened with significance. Dying patients showed markedly decreased blood pressure, cyanosis, cold extremity, death rattle, abnormal respiration frequently at 48hours before death. Conclusions: Terminally ill cancer patients have various prognostic factor and the most important factor is performance status. The death predictive symptoms such as markedly decreased pressure, cyanosis, cold extremity, death rattle, abnormal respiration appeared at last 48hours. If we assess the symptoms more carefully, we can predict the more accurate prognosis. The communication about the prognostic information will influence the personal therapeutic decision and specific care planning. No significant financial relationships to disclose.
Distress and breast cancer anxiety (BCA) among BRCA mutation carriers participating in MRI-based screening
Authors: Hill K. , Warner E. , Esplen M. , Bigenwald R. 
Published: March 2020

20001 Background: MRI has consistently been shown to be a more sensitive screening tool than mammography (M) but its lower specificity could have negative psychological effects. In a pilot study (SABCS 2004) no adverse psychological effects of MRI screening were found. A larger study was then done to look particularly at the impact of imaging recalls and biopsies. Methods: BRCA mutation carriers having breast screening with annual M, MRI, and ultrasound (US) + 6monthly clinical breast examination (CBE) were asked to complete questionnaires: 1 - 2 wks pre, 4 - 6 weeks after, and 6 months after their imaging. Questionnaires included the hospital anxiety and depression scale (HADS), a modified Kash breast cancer anxiety scale (BCAS), the monitor/blunter scale, a rating of overall health on a linear analog scale, a 4 category rating of anxiety related to each screening modality, and a description of any recent life altering events. Results: 54 women (29 BRCA1, 25 BRCA2) completed at least 2 questionnaires (median 3, range 2–5). Mean age was 44 (range 28–64). 26% were surveyed during their 1st round of screening. There was a very strong correlation between the BCAS and HADS anxiety with 19 (35%) having baseline BCA of whom 15 (79%) were monitors compared to 60% monitors among the patients without BCA. At baseline 41 (76%) indicated moderate/high MRI related anxiety compared to 61%, 46%, and 43% for M, U/S and CBE. Of the 16 patients (30%) who had recalls ± biopsy (n = 5) while on this study, 10 (63%) had elevated BCA and 3(19%) increased depression at baseline. In all but 2 women whose anxiety increased due to life events, no scores changed significantly after recall or biopsy. Only 1 cancer was diagnosed during the study period. In the other 38 women scores changed significantly only as a result of life events. Conclusions: Despite a high false positive rate, MRI-based screening had no detectable adverse psychological effects on BRCA mutation carriers in this study. No significant financial relationships to disclose.
Prognostic significance of plasma Epstein-Barr virus (EBV) DNA level in patients with locally advanced head and neck carcinoma treated with concurrent cisplatin and concomitant boost radiotherapy (CBRT)
Authors: Yu K. H. , Chan A. K. , Tse G. M. , Kam M. K. , Hui E. P. , King A. D. , Vlantis A. C. , Wong K. T. , Lo D. Y. , Chan A. T. 
Published: March 2020

20003 Background: EBV DNA is detectable in the plasma in most patients (Pts) with lymphoepithelial carcinoma (LECA) and in some Pts with squamous cell carcinoma (SCC) of the HN. We investigated the prognostic significance of plasma EBV DNA level in a prospective phase II trial of concurrent cisplatin and CBRT for locally advanced HN carcinomas. Methods: Eligibility criteria included newly-diagnosed SCC or LECA of non-nasopharyngeal HN sites; stage III or IV disease; ECOG performance status ≤ 1; and age ≤ 70 years. Plasma EBV DNA levels were measured by real-time quantitative polymerase chain reaction (PCR) before treatment and at 6 weeks post-treatment. Pre-treatment gross tumor volume (GTV) was measured on CT, and invasion of bone and cartilage was assessed on CT and MRI. Cisplatin 40–50 mg/m2 was given on days 1, 8, 15 and 22 of CBRT. Radiotherapy consisted of 54 Gy/30 fractions/6 weeks and a concomitant boost (18 Gy/12 fractions) in the last 12 treatment days. The primary endpoint was overall survival (OS) and the secondary endpoint was progression-free survival (PFS). Survival curves were compared by the log-rank test and multivariate analysis was performed with Cox regression. Results: Between March 2001 and January 2005, 46 Pts were recruited (36 with SCC and 10 with LECA). Thirty-four Pts had stage III and 12 had stage IV disease. Pre-treatment plasma EBV DNA level was > 0 copy/ml in all Pts with LECA (range, 37 - 211737 copies/ml) and in 8 Pts with SCC (range, 10 - 48734 copies/ml). Ten Pts had plasma EBV DNA level > 0 copy/ml at 6 weeks post-treatment. With a median follow-up of 1.6 years, the 1-year OS rate was 87.7 % and 1-year PFS rate was 68.3%. On multivariate analysis, plasma EBV DNA > 0 copy/ml at 6 weeks post-treatment was the only independent predictive factor of decreased OS [hazard ratio (HR) 3.59, p = 0.04] for the entire group. In the subgroup of Pts with SCC, pre-treatment EBV DNA > 0 copy/ml was the only independent predictive factor of decreased locoregional PFS (HR 7.08, p = 0.03). Conclusions: Plasma EBV DNA level is a prognostic factor in Pts with locally advanced HN SCC and LECA. Further studies are warranted to confirm the finding and to elucidate its biological basis. No significant financial relationships to disclose.
Breast cancer risk estimates using the Gail Model in women from an annual screening program in Southern Brazil
Authors: Belo Reyes V. , Skonieski G. , Zignani J. , Bedin A. , Giugliani R. , Palmero E. I. , Kalakun L. , Schuler-Faccini L. , Ashton-Prolla P. , Caleffi M. 
Published: March 2020

20045 Background: The Gail model is widely used to estimate breast cancer (BC) risk. It has been validated as a reliable risk predictor in North America, but very few studies have been done in other countries. This study intends to examine the estimated BC risk using the Gail Model in a sample of women from Southern Brazil a region with the highest BC incidence and mortality rates of the country. Methods: Lifetime and 5-year BC risk estimates were obtained for the first 1002 asymptomatic women (ages 40–69 years) enrolled in an annual BC screening program. The frequency of each of the model’s variables was recorded and compared to other studies. Information about family history (FH) included: presence of bilateral BC, male BC, first degree relative with BC and/or ovarian cancer (OC), relative with BC under age 50 and ≥ 2 relatives with either BC, OC or colorectal cancer (CRC). Other potential risk factors for BC such as body mass index and smoking were recorded. Results: Mean (± SD) values for age, age at menarche and age at birth of the first live child were 50.4 (± 7.75), 13.0 (± 1.80), and 21.6 (± 5.00) years, respectively. Only 50 (5.0%) women were nulliparous and 62 (6.2%) reported their first live birth after age 30. History of at least one first-degree relative (FDR) affected with BC was reported by 52 (5.2%), and 31 (3.1%) had a previous breast biopsy. The mean estimated BC risk in 5 years was 0.92% (± 0.49); for those under age 60, 24 (2.8%) had an estimated 5-yr risk over 1.66%. The mean estimated lifetime BC risk was 7.80 (± 3.2). Interestingly, a history of cancer in a FDR was reported by 32.6% of the women, and evidence of familial BC was observed in 20.4%. The estimated BC risk using the Gail model was significantly higher in women with a family history of BC < 50ys and with ≥ 2 relatives with either BC, OC or CRC. Smoking and overweight were reported by 28% and 65% of the women, respectively. Conclusions: BC risk estimates obtained with the Gail Model did not differ significantly from those described in other populations. However, specific findings in cancer FH were associated with higher risk estimates. The importance of FH and overweight will be further explored in a larger sample. Population-specific risk factors for BC should be sought in different communities to ensure proper risk estimates. No significant financial relationships to disclose.
Evaluation of HER-2 in serum and tissue: correlation with clinical-pathological parameters and outcome in early stage breast cancer (BC) patients (pts)
Authors: Ludovini V. , Gori S. , Mosconi A. , Pistola L. , Rulli E. , Rulli A. , Anastasi P. , Pacifico E. , Sidoni A. , Tofanetti F. R. , Colozza M. 
Published: March 2020

20066 Background: HER2 is amplified and/or overexpressed in approximately 20–30% of invasive BC and is associated with poor prognosis. It is also a predictive marker of response to trastuzumab. The extracellular domain of the HER2 protein (sHER2) is frequently cleaved and released into the circulation where it can be detected by ELISA in up to 45% of advanced BC. We evaluated HER2 expression in paired serum and tissue samples of operable BC pts to analyze 1) the correlation between sHER2 and HER2 tumor status 2) their relationship with clinical-pathological parameters and 3) their impact on the outcome. Methods: 188 consecutive stage I-III BC pts were included in this study from May 2000 to July 2005. sHER2 was measured by ELISA (manual Kit “Oncogene Science Diagnostics” and automated version “ADVIA Centaur”) before the local treatment. Tumor tissue was analyzed by IHC with CB11 antibody and scored with Dako Hercept-test. HER2 amplification was determined using the Ventana FISH assay in patients with 2+ by IHC. Chi-squared test was used to evaluate the association between HER2 and patients’ clinical-pathological features. Survival outcomes were analyzed using Cox’s model. Results: Median age was 56.6 years; 122 pts received adjuvant chemotherapy, 54 endocrine therapy and 83 both. Forty-three pts (23%) had HER2 overexpression/amplification in tumor tissue and 25 pts (13%) had sHER2 levels ≥15 ng/ml (cut-off level) with a concordance of 85%. Both high sHER2 levels and HER2 tumor expression were associated with high histological grade (p = .02 and p < .0001 respectively) and negativity of ER (p = .0035 and p < .0001) and PgR (p = .0056 and p =. 002). At a median follow-up of 2.4 years we observed 8 deaths and 19 relapses. At univariate analysis high sHER2 levels (evaluated as continuous variable) were significantly correlated with shorter DFS (p = 0.0002) even if at multivariate analysis high sHER2 levels, after adjustment for stage and ER status, were associated with a shorter DFS with borderline significance (p = 0.06). Conclusion: Our preliminary data indicate that the evaluation of sHER2 at diagnosis defines a small subgroup of early BC pts with a poor prognosis even if it needs to be confirmed in a longer follow up. No significant financial relationships to disclose.
Phase I study of intravenous (IV) milataxel in adult patients with advanced malignant tumors
Authors: Bourbouloux E. , Campone M. , Vermorken J. B. , Martin M. , Sessa C. , Perotti A. 
Published: March 2020

2037 Background: M (TL139, MAC-321) is a novel taxane with activity in human xenograft models against tumors resistant to paclitaxel. The maximum tolerated dose (MTD) when given IV every 3 weeks was 35 mg/m2. The current study was designed to determine if the dose intensity of M could be increased by a weekly IV schedule. Methods: The primary objective of the study was to determine the maximum tolerated dose (MTD), the dose limiting toxicity (DLT) and the recommended dose (RD) for phase II. Secondary objectives were pharmacokinetic (PK)/pharmacodynamic (PD) parameters of M given IV weekly and a preliminary estimate of efficacy in an expanded cohort at the RD. Key pt eligibility criteria included in adult pts with refractory malignant tumors, ECOG PS <3 and adequate hematologic, hepatic and renal function. Patients were not allowed concurrent strong inhibitors of cytochrome p450 3A4. Dose escalation was based on Fibonacci method. At the RD, additional pts with tumors that typically respond to taxane treatment were added. PK data were obtained on day 1 and 15. Results: A total of 32 pts were treated, 15 (6 females, 9 males) in the dose escalation part and 17 (15 females, 2 males) in the MTD confirmation part. The median number of doses was 11 (range 1–18). In the dose escalation phase, 3, 4, and 3 pts were treated at 8, 12, and 16 mg/m2 IV weekly without DLT. At 20 mg/m2, 2 of 5 pts developed DLT (1 pt - myalgia and neuropathy, 1 pt grade 4 neutropenia > 5 days in duration). The RD was 16 mg/m2 weekly. 17 more pts were treated at the RD. The most frequent grade 3 or 4 adverse events were asthenia (19%), nausea (9%), parethesia (9%) and neuropathy (9%). Of the 10 pts with breast cancer who were evaluable for response, one had a PR. Another breast cancer pt with a PR was a protocol violation and was not evaluable. In 20 pts at the MTD, the Tmax was 4 hr, the Cmax was 51.97 ng/mL, AUC 2711 ng*hr/mL, and the Vss was 1496 L/m2. Conclusions: Milataxel had an RD of 16 mg/m2 IV per week. Objective responses were observed in pts with metastatic breast cancer. No significant financial relationships to disclose.
Therapeutic activity of neutralizing monoclonal antibodies targeting hepatoma-derived growth factor in cancer xenograft models
Authors: Mao L. , Ren H. , Chu Z. , Yuan P. 
Published: March 2020

2517 Background: Hepatoma-derived growth factor (HDGF) is a mitogen for endothelial cells, vessel smooth muscle cells, fibroblasts, as well as some epithelial cells. It is overexpressed in a number of human cancers and its overexpression in tumors strongly correlates with tumor progression, recurrence, and metastasis. We recently showed that down-regulation of HDGF in lung cancer cells reduces tumorigenecity in both in vitro cell and in vivo animal models suggesting HDGF may be of a therapeutic target for cancer. Methods: Recombinant HDGF was used to develop a panel of monoclonal antibodies specifically bind to HDGF. Four antibodies were tested for their therapeutic activity in lung and pancreatic cancer xenograft models. The monoclonal antibodies were administered 250μg/animal (5 mice per group) every 3 days IP when the subcutaneous tumors reached approximately 50 mm3. Results: Two antibodies (C1 and H3) exhibited significant therapeutic activity in A549 lung cancer model whereas H3 also showed a therapeutic effect in MiaPaca-2 pancreatic cancer model. No sign of toxicity in the living animals and histology of major organs were observed in the antibody treated animals. In the A549 model, the mean tumor burden was 960 mm3 for control-IgG treated mice 22 days after tumor inoculation, whereas the mean tumor burdens were 224 mm3 for C1 and 266 mm3 for H3 treated mice (P < 0.05) respectively. In the MiaPaca-2, the mean tumor burden was 994 mm3 for control-IgG treated mice 21 days after tumor inoculation in contrast to 345 mm3 for H3 treated mice (P < 0.05). Consistent with known biologic functions of HDGF, our early morphologic and biomarker analyses suggest that H3 may neutralize tumor cell released HDGF resulting in disruption of tumor stroma and extracellular matrix structures. Conclusions: HDGF is a novel therapeutic target for multiple human cancers and neutralizing monoclonal antibodies targeting HDGF are effective in treating lung and pancreatic cancers in animal models. (Supported by DoD grant DAMD17–01–1-01689–1) No significant financial relationships to disclose.
Efficacy of SMIP-016, a novel CD37-directed biologic therapy, in human NHL tumor xenograft models
Authors: Barone D. S. , Nilsson C. , Ledbetter J. , Hayden-Ledbetter M. , Mohler K. 
Published: March 2020

2565 Background: Small Modular Immuno-Pharmaceuticals (SMIP) biopharmaceuticals belong to a novel proprietary biologic compound class that retain Fc mediated effector functions and are smaller than monoclonal antibodies. SMIP-016 is a SMIP product candidate that binds to CD37 on human B cells and has potent ADCC and apoptotic activity in vitro. CD-37 is known to be over-expressed in non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL). We have evaluated the activity of SMIP-016 in established human tumor xenograft models in nude mice. Methods: Nude mice were injected subcutaneously with either Ramos or Daudi tumor cells. At approximately 7 days post tumor inoculation the mice were randomized to groups with roughly equivalent mean tumor volumes (>200mm3) and were treated with SMIP-016 or rituximab as a comparator. Groups were evaluated for median survival time (MST), tumor volume and percentage of tumor-free animals. Results: In nude mice bearing Daudi tumors, SMIP-016 treated mice showed a significant improvement in MST compared to control mice (p < 0.0001). Nude mice bearing Ramos tumors treated with SMIP-016 also demonstrated a significant enhancement in their median survival time (MST) in comparison to control mice (p < 0.0001). In addition, mice receiving SMIP-016 administered in combination with rituximab in this model demonstrated improvements in survival time over either single agent therapy alone. Conclusions: SMIP-016 is effective in treating established tumors in these human tumor xenograft models. Addition of SMIP-016 to rituximab therapy resulted in enhanced survival times compared to animals treated with rituximab alone. [Table: see text]
Phase 1 pharmacokinetic and pharmacodynamic study of the histone deacetylase inhibitor MS-275 in combination with 13-cis retinoic acid in patients with advanced solid tumors
Authors: Pili R. , Rudek M. , Altiok S. , Qian D. , Zhao M. , Donehower R. , Anderson A. , Halter M. , McFarland H. , Zwiebel J. , Carducci M. 
Published: March 2020

3055 Background: Preclinical studies suggest that histone deacetylase (HDAC) inhibitors may restore tumor sensitivity to retinoids. The objective of this study was to determine the maximum-tolerated dose (MTD), the dose-limiting toxicity (DLT), and the pharmacokinetic (PK)/pharmacodynamic (PD) profiles of the HDAC inhibitor MS-275 in combination with 13-cis retinoic acid (CRA). Methods: Patients (pts) with advanced solid tumors were treated with MS-275 orally once weekly and CRA orally twice daily x 3 weeks every 4 weeks. The starting dose for MS-275 was 4 mg/m2 and the dose was escalated based on toxicity assessments. The fixed dose for CRA was 1 mg/kg/day. PK concentrations of MS-275 and CRA were determined by LC/MS/MS. Western Blot analysis on peripheral-blood mononuclear cells (PBMCs) and tumor samples (when feasible) were performed to evaluate target inhibition. Results: To date thirteen pts have been enrolled. Tumor types include prostate (4 pts), bladder and renal cell (2 pts), and others. The MTD was exceeded at the 5 mg/m2 dose level (G3 hyponatremia, neutropenia and anemia). Fatigue (G1 or G2) is a common side effect. MS-275 peak concentrations were 141.6±75.7ng/mL at 4mg/m2 and 139.5±30.9 ng/mL at 5mg/m2. MS-275 half-life and clearance were 108.2±47.9h and 9.4±6.0L/h/m2, which is consistent with prior reports for MS-275 as single agent. Median CRA steady-state trough levels were 182.4 ng/mL. The MTD was 4 mg/m2 MS-275 and 1 mg/kg CRA. Five pts remained on treatment for ≥ 4 months including pts with prostate cancer (3), pancreatic cancer (6 months) and a pt with renal cell carcinoma (12 months) who presented a partial response in the lungs. Histones isolated from PBMCs showed transient but consistent protein acetylation post-therapy. Tumor biopsy of a liver lesion from prostate carcinoma revealed post-therapy induced histone acetylation and decreased phosphorylated ERK and STAT3 protein expression consistent with HDAC inhibitory activity. Conclusions: Combination of MS-275 with CRA is reasonably well tolerated and 4 mg/m2 is the Phase II recommended dose for MS-275 in combination with CRA. Tumor response and PD data suggest clinical and biological activity for this combination strategy. [Table: see text]