bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteonecrosis of the jaw and bisphosphonate therapy: Experience from a single Italian institution
Authors: Collovà E. , Paulli S. , Morabito M. , Frattini D. , Martelli O. , Fava S. 
Published: March 2020

19661 Background: Osteonecrosis of the jaw (ONJ) is reported as serious side-effect after bisphosphonate (B) therapy. Although the number of patients (pts) presenting with ONJ seems to be increasing, the exact prevalence and etiology of osteonecrosis are not well established because of heterogeneous of clinical reports. Methods: From May 2005 and October 2006, 12 cases of ONJ were diagnoses at our Institution. Results: Characteristics of patients: the median age at presentation of ONJ was 64.2 years (range 43–79); 9 pts were female and 3 pts were male. All pts were treated with Zoledronic acid, none of pts were pretreated with other B. Location of necrosis was mandible and maxilla. Presenting symptoms were: parondotosis disease, bone exposure and ulceration. Osteonecrosis was preceded by dental extraction in 5 pts (45%). The diagnosis of ONJ was: clinical (exposed bone) and radiological in all pts; the biopsy was performed in 3 pts, none of wich showed the presence of neoplastic disease. The treatments of ONJ were: antibiotic in 3 pts, partial maxillectomiy in 2 pts, curettage in 8 pts. Only 1 pts was documented residual sites of necrosis after surgical malignancies. All pts are alive at the time of this report, with except of one. Characteristics of malignancies: breast cancer 7 pts, prostate cancer 2 pts, multiple myeloma 1 pts, carcinoma of unknown primary 1 pts. Concomitant or previous therapies for malignancies were: chemotherapy and/or radiotherapy in all pts. None of pts received radiotherapy to the involved region. B therapy has been continued in about half pts, irrespective previously ONJ, without worsening clinical condition. Conclusions: In our experience the number of pts with previous history of dental extraction and subsequent ONJ during B therapy is consistent as described in many reports. This condition may represent an important risk factor for developing osteonecrosis correlated with prolonged infusion of B. In order to reduce incidence and serious side effects of B therapy, we adopted alternative schedule treatment with bi or tri - monthly infusion. No significant financial relationships to disclose.
Participative design of a support questionnaire for the process of diagnosing anorexia-caquexia syndorme (ACS) in cancer patients
Authors: Valentín V. , Casas A. , Carulla J. , Camps C. , Baron M. Gonzalez , Lizón J. , Sanz J. , Iglesias L. , Covas A. , Pisa S. 
Published: March 2020

19662 Background: Early treatment of the anorexia-cachexia syndrome (ACS) provides a significant benefit for cancer patients, hence the need for early diagnosis. Currently available tools are complex, hampering their systematic application in clinical practice and treatment does not begin until moderate-to-severe states of malnutrition are reached. After holding 20 workshops between 2003–2005 involving about 150 Spanish oncologists, it was concluded that the ACS diagnosis should be based on questionnaires, anthropometric assessment and analytical determination, hence the need for design a brief and efficient questionnaire to support the process of diagnosing ACS in cancer patients. Methods: Between February and June 2006, 9 working sessions were held and 123 oncologists consulted to assess the symptoms and diagnostic tests required for the evaluation of ACS. In all sessions a preliminary presentation was given on the conclusions of the workshops held over the previous two years, followed by a structured discussion that was facilitated by a moderator using the Metaplan work method. Results: Questions achieving a consensus of over 75% were deemed as essential. Included among the questions to be answered by the patients are: anorexia (79.7%), dysphagia (78.9%) and vomiting/nausea (79.7%). The physician’s set of questions include: evolution of body weight determined by weight loss >10% (94.3%); stage of the disease (80.5%), considering stage IV to be an alert sign of ACS; the location of the neoplasia (78.9%), with head and neck, esophagus, pancreas, biliary ducts and stomach being the most prevalent neoplasia locations among these patients and albumin level (77.2%), being suspected ACS diagnosis on 2.1 mg/dl or less. It was agreed that the questionnaire should be a simple tool, phrased in easy-to- understand language and formulated with short (92%) and few (85%)questions and to keep the format simple, making it easier to fill in (36.5%). The inclusion of closed “Yes/No” type answers was regarded positively. Conclusions: The proposed ACS diagnosis questionnaire meets the expectations set at the start of the project. We are currently carrying out a validation process in order to ensure its reproducibility. No significant financial relationships to disclose.
The utility of assessing physical activity in ovarian cancer patients following chemotherapy
Authors: Zakashansky K. , Higgins S. , Montgomery G. , Dottino P. , Bovbjerg D. 
Published: March 2020

19666 Objective: The purpose of this preliminary study was to explore the utility of objective assessments of physical activity for investigating the patterns and predictors of reduced physical activity levels in patients receiving standard chemotherapy for ovarian cancer. Methods: Ovarian cancer patients receiving standard regimens of Taxol/Carboplatin chemotherapy (n=9) were recruited prior to their treatment infusion. After signing informed consent, they completed the 20-item Center for Epidemiologic Studies Depression Scale (CESD); post treatment daily activity levels were assessed with a wrist watch-sized, water proof, omnidirectional, actigraphy monitor (Actiwatch-64, Mini Mitter, Bend, OR) worn on the nondominant wrist for the three weeks between treatment cycles. Identical actigraphy data were collected on a sample of healthy female staff (n=9) over a 1 week interval to provide a benchmark for comparison. Results: As expected, waking activity levels in the control sample showed no significant changes across days (p=0.41), so mean levels (343.45 counts) and 95% confidence intervals were calculated for comparison purposes. Chemotherapy patients had significantly lower levels of activity, as well as evidence of recovering physical activity over the 21 days following treatment (p=0.01). Interestingly, the subset (n=4) of patients with higher levels of pretreatment depression (Hi-CESD) did not show significant recovery in physical activity while the Lo-CESD subgroup showed substantial recovery (p=0.001). Conclusions: Objective assessment of physical activity in ovarian cancer patients following chemotherapy treatment reveals significant reduction in activity levels, and a failure to recover in patients with higher levels of pretreatment depression. Actigraphy of daily activity levels may provide a sensitive means of quantifying reductions in physical activity and recovery patterns following chemotherapy treatment for gynecologic cancer. No significant financial relationships to disclose.
Assessment of safety with abbreviated, weight-based bevacizumab infusions in a variety of solid tumors
Authors: Hart J. W. , Murillo J. R. , Oholendt M. S. , Preti H. A. 
Published: March 2020

19674 Background: Bevacizumab (BEV), a humanized monoclonal antibody that neutralizes vascular endothelial growth factor, has shown improved responses in patients with colorectal cancer (CRC) and non-small cell lung cancer (NSCLC) while displaying activity in a variety of other solid tumors. Phase I clinical trials with BEV utilized standard 90- 60-, and 30-minute infusions for 1st, 2nd, and subsequent infusions, as tolerated; initial doses reported less than 3% incidence of infusion-related adverse events (AEs), with 0.2% grade III/IV reactions. Recommended infusion rates for BEV remain unchanged despite the minimal risk of infusion-related AEs. Saltz and colleagues recently reported novel data supporting the safety and tolerability of abbreviated BEV infusions in CRC patients within a single institution. Our objective was to replicate previously reported safety profiles while utilizing abbreviated infusions of BEV in multiple tumor types. Methods: An internal retrospective analysis revealing minimal infusion AEs with standard infusions facilitated this current study. BEV- naïve and previously-treated patients were consented for the study utilizing the following weight-based infusion times: 5, 10, and 15 mg/kg doses over 10, 20, or 30 minutes, respectively, for all doses. Patients were assessed throughout and immediately following the infusion for any infusion-related AE. Results: A variety of tumor types are represented in 26 enrolled patients including CRC, NSCLC, breast, ovarian, pancreatic, and brain. Central nervous system involvement accounted for 35% of patients [primary brain (23%) and metastatic disease (12%)]. A considerable number of patients (19%) were treated with single-agent BEV. Nine BEV-naïve patients were initiated on abbreviated infusions, while 16 were converted from the standard infusion schedule. Seventy-seven total doses utilizing the abbreviated infusions failed to produce infusion-related AEs. Conclusion: These results support previous data affirming the safety and tolerability of abbreviated BEV infusions in CRC patients, while also reporting promising safety of abbreviated infusions in a variety of additionally unreported solid tumors types. No significant financial relationships to disclose.
Promoting evidence-based management of anemia in cancer patients: Background and scientific validation of RESPOND, a web-based clinical decision support system
Authors: Van Erps J. , Aapro M. , MacDonald K. , Soubeyran P. , Muenzberg M. , Dunlop R. , Eeckhout C. , Warrinnier H. , van Well M. , Abraham I. 
Published: March 2020

19676 Background: The 2006 European Organisation for Research and Treatment of Cancer (EORTC) guidelines for erythropoietic proteins in cancer-related anemia provide the most up-to-date assessment of the evidence base. To promote clinicians’ adoption of evidence- based (EB) practice guidelines (EBPGs), it is critical to bring guidelines to the point of care. RESPOND is an EB clinical decision support system (CDSS) based on the EORTC guidelines. CDSSs are seldom validated. We describe the methodologies of two studies being conducted to validate RESPOND. Methods. Study 1: descriptive design - accuracy and content validity. Five experts are asked to rate the accuracy of algorithms derived from the guidelines; the objective being an intraclass correlation coefficient =0.90 for each of 27 algorithmic sets. Study 2: hybrid matched pre-post design - concurrent and discriminant validity. Two patient cohorts (n=33 each) matched by type of cancer and similarity of chemotherapy regimen ie, sample 1 (4 months prospective data after RESPOND [post]) and sample 2 (4 months retrospective data prior to RESPOND [pre]) were used to test concurrent validity (congruence scores [CS] of sample 1) and discriminant validity (difference between sample 2 and sample 1 CS). A score is calculated for each patient to quantify the extent to which treatment and outcomes are congruent with the EORTC EBPG. Table 1 . Calculation of the congruence score ESA, erythropoiesis-stimulating agent; Hb, hemoglobin, Q1W, once weekly, Q3W, once every three weeks Conclusions. These studies will provide the necessary validation for RESPOND as an evidence-based clinical support tool. [Table: see text] [Table: see text]
A randomised prospective study of prolonged treatment with tocopherol and pentoxifylline, in addition to carbogen in the management of radiation late effects
Authors: Brennan S. M. , O Shea C. , Salib O. , Moriarty M. 
Published: March 2020

19682 Background: Pentoxifylline (PTX) and tocopherol (Vitamin E) are antioxidants previously shown to be useful in combination in the treatment of late radiation effects. To our knowledge, this is the first study to examine the clinical benefit of combination therapy with carbogen, tocopherol and pentoxifylline in the mitigation of late radiation effects. The optimal duration of PTX and tocopherol treatment has not been fully established. Therefore, we also studied short versus extended treatment duration. Methods: We conducted a phase II prospective randomised study of inhaled carbogen (95% oxygen + 5% carbon dioxide) over 90 minutes, 5 days per week for 3 weeks in addition to short versus prolonged treatment with pentoxifylline (800 mg) and tocopherol (1,000 IU) orally once daily. All 18 patients received carbogen therapy. Patients with grade 3 toxicity post radical radiotherapy for a variety of cancer primaries were eligible for the trial. The primary endpoint was improvement in maximum Lent-Soma toxicity scores. Ethical approval was obtained. Results: Maximum Lent-Soma scores improved with treatment in six of the eighteen patients giving a 33% response rate. The proportion of patients responding to treatment in the prolonged treatment arm B was more than double than in the shorter arm A (Fisher’s exact test: p = 0.321). Two patients in arm B had complete resolution of their symptoms, which was maintained at 2 and 3 years follow up. Conclusions: As late radiation effects are progressive by nature and have such a negative impact on quality of life in long-term cancer survivors, any treatment, which may ameliorate their symptoms, should be considered of benefit. This study confirms the benefit of prolonged treatment and we would recommend clinical use of these agents with treatment duration of at least 12 months, in the management of late radiation effects. No significant financial relationships to disclose.
Clinical outcome of chemoradiotherapy in elderly patients with non-small cell lung cancer at G.V Montgomery Veterans Affairs Medical Center
Authors: Choi M. , Chan W. , Jaiwatana J. , Khansur T. 
Published: March 2020

19683 Background: More than 2/3 of lung cancer patients are age = 65 and the proportion of elderly patients are expected to rise in the United States. However data on the use of optimal chemoradiotherapy in this group of patients are limited. Methods: All lung cancer patients = 65 years, who received both chemotherapy and radiation therapy at the G. V. Montgomery VAMC between Jan 2000 to Dec 2005, were analyzed from tumor registry and computerized medical records. Patients who only received palliative radiation therapy for bone and brain metastasis were excluded. Results: Among 652 lung cancer patients diagnose, 46 patients = 65 years received both chemotherapy and radiation therapy over the 6 year study period. The median age was 72 (range:65–84) and 70% of the patients were = 70 years. All patients were male with 65% white and 35% black population. The majority of patients were stage III (85%) while there was one stage I and six stage II patients. 41 patients (89%) were able to complete the planned radiation therapy and median dose delivered was 6140 cGy. The chemotherapy regimen was carboplatin and paclitaxel either weekly during radiation therapy and every three weeks in sequential treatment. There was only 1 treatment related mortality and only 15% of patients survived less than 6 months. The 1, 2, 3 year survival rates were 67%, 24%, and 15% respectively and median survival was 15.3 months. 15 patients were treated sequentially(S) with chemotherapy (median cycle-3) followed by radiation therapy and 31 patients concurrently (C) with chemoradiotherapy. (median- 5 weekly treatment) The survival among the two groups did not differ statistically. (median survival-19.1 month (S) vs. 14 month (C) p=0.78) Conclusions: Both sequential and concurrent chemoradiotherapy is feasible and beneficial in elderly patients with lung cancer. Sequential treatments might be as effective as concurrent chemoradiotherapy in elderly VA patient population. No significant financial relationships to disclose.
Phase I/IIa trial of cilengitide (EMD121974) and temozolomide with concomitant radiotherapy, followed by temozolomide and cilengitide maintenance therapy in patients (pts) with newly diagnosed glioblastoma (GBM)
Authors: Stupp R. , Goldbrunner R. , Neyns B. , Schlegel U. , Clement P. , Grabenbauer G. G. , Hegi M. E. , Nippgen J. , Picard M. , Weller M. 
Published: March 2020

2000 Background: To evaluate safety, toxicity, and efficacy of the combination of the cyclic RGD pentapeptide cilengitide (EMD121974), an inhibitor of integrins avβ3 and avβ5, in addition to standard temozolomide (TMZ) and radiotherapy (RT). Methods: 52 pts (PS 0–1: 92%, 2: 8%; median age 57 yrs) after tumor resection (n=43/83%) or biopsy (n= 9/17%) were treated with standard TMZ/RT (Stupp et al. NEJM 2005). In addition cilengitide (500 mg i.v., 2x/week) was started one week before TMZ/RT and given throughout for the duration of chemotherapy or until progression. The primary endpoint was progression free survival rate at 6 months (target: 65%). Pts were followed with MRI every 2 months. Histopathologic diagnosis and MRI imaging were independently reviewed, O6-Methylguanine- DNA methyltransferase (MGMT) promotor methylation status was assessed in 45 (86.5%) pts. Results: 46 pts (92%) completed RT, = 90% of concomitant TMZ was received by 42 pts and cilengitide by 45 pts. 20 pts (3 ongoing) completed 6 cycles of maintenance TMZ and cilengitide. Observed hematological grade 3 and 4 toxicities were: lymphopenia (28/52, 53.8%), thrombocytopenia (7/52 pt. 13.4%) and neutropenia (5/52, 9.6%). Treatment related non-hematologic grade 3/4 toxicities were reported for n=3/52 (5.7%) patients: constitutional symptoms (asthenia, fatigue, anorexia, n=3); elevated liver function tests (n=1), deep venous thrombosis and pulmonary embolism (n=1). One patient with a history of sigmoid diverticulosis experienced sigmoid perforation (grade 2). In total, 34/52 (65.4% [95% CI, 50.9–78.0%]) of the pts were progression free at 6 months. Pts with MGMT gene-promotor methylation in the tumor were more likely to reach 6 months PFS endpoint. Conclusions: The study reached its primary endpoint. The combination of the integrin inhibitor RGD peptide Cilengitide and TMZ/RT was well tolerated, PFS at 6 months is encouraging. MGMT gene promoter methylation correlates with outcome. At the time of ASCO, updated results and survival estimates after a minimum follow-up of at least 1 year will be available. [Table: see text]
The role of EGFR trafficking in neuroblastoma
Authors: Zage P. E. , Yan Q. , Zeng L. , Bean A. J. 
Published: March 2020

20003 Background: Signaling through growth factor receptors is important in neuroblastoma pathogenesis. Chromosome 1p36 is commonly deleted in neuroblastoma tumors and is associated with a poor prognosis. UBE4B, a gene in 1p36, has been reported mutated in high- risk neuroblastoma. We have found a direct interaction between UBE4B and hrs, a protein required for epidermal growth factor receptor (EGFR) trafficking, suggesting a link between EGFR trafficking and neuroblastoma pathogenesis. We have analyzed the role of UBE4B in the EGFR pathway in neuroblastoma cell lines. Methods: The expression of UBE4B, hrs and EGFR were analyzed by quantitative Western blot in a panel of 7 human neuroblastoma cell lines (SHEP, SKNAS, SKNSH, KCNR, SY5Y, LA155N, NGP). EGFR degradation rates were determined by examining the kinetics of cellular EGFR depletion following a pulse of ligand. Results: UBE4B levels were lowest in SKNAS and highest in NGP cells. Hrs levels were lowest in SKNSH cells and higher in other cell lines. EGFR levels were lowest in NGP and KCNR and highest in SKNAS cells. UBE4B levels were correlated with known 1p deletions. EGFR degradation rates were slowest in SKNAS cells and therefore correlated with cellular UBE4B levels. The low degradation rates were correlated with high cellular levels of EGFR. Conclusions: Expression levels of UBE4B are correlated in neuroblastoma cell lines with chromosome 1p deletions. Cell lines with lower levels of UBE4B degrade EGFR at a markedly slower rate, correlated with higher cellular EGFR levels. We hypothesize that UBE4B affects cell growth by interacting with hrs, directing EGFR for degradation. In its absence the ability of a cell to sort growth factor receptors for degradation is inhibited, resulting in growth factor receptor overabundance and uncontrolled cell growth. These results support the testing of EGFR inhibitors in a future phase I trial for children with neuroblastoma. No significant financial relationships to disclose.
Chemotherapy plus cyclosporine A for the treatment of intraocular retinoblastoma: The University of Miami Miller School of Medicine experience
Authors: Fernandes C. E. , Schefler A. C. , Murray T. G. , Davis J. A. , Alvarez O. A. , Podda A. , Barredo J. C. , White E. , Lewis N. , Toledano S. R. 
Published: March 2020

20005 Background: In the past decade chemotherapy and focal control became the standard of care in retinoblastoma. The ideal chemotherapy regimen has not yet been determined. We analyzed the results of treatment at the University of Miami Miller School of Medicine using the regimen carboplatin (20 mg/kg, day 1), vincristine (0.05 mg. /kg, day 1), etoposide (5 mg / kg, days 1 and 2) with or without cyclosporine A (10 mg. /kg over 2 hours followed by 45 mg/kg over 31 hours) every 3–4 weeks. We attempted to maintain peak CSA levels between 2,400 and 6,000 and steady state levels between 2,400 and 4,200 ng/ml. When CSA was given, vincristine was started at 0.0125 mg /kg. The dose was escalated by 25% with each cycle of therapy, as tolerated. Methods: A retrospective analysis was performed in 41 patients diagnosed with bilateral retinoblastoma from Dec 1996 to Jan 2006. Only eyes with intraocular disease (76 eyes) were included in this analysis. Before each cycle of chemotherapy ophthalmologic examination under anesthesia was performed and active tumor and seeding were treated with local ablation using laser therapy. Eyes in which enucleation was planned at diagnosis were excluded from this analysis. Results: Most patients received 9 cycles of chemotherapy. Sixty percent (46/76) of the eyes were treated with chemotherapy and CSA. The eye salvage rate for eyes classified by the International Classification of Retinoblastoma (ICRB) as groups A, B, C and D was 100%. The eye salvage rate for the 21 eyes classified as ICRB group E was 29%. No difference in salvage rate was observed in eyes treated with or without CSA. One patient died from disease progression. Only one patient required radiation therapy to both eyes. To date there have been no reports of development of secondary malignancies. Conclusion: The addition of CSA to the treatment of the eyes classified as ICRB groups A, B, C and D made no difference in the eye salvage rate. Also, we were not able to demonstrate any benefit from the addition of CSA in patients with stage E eyes- although our sample size was quite small. Aggressive focal control and chemotherapy beginning at diagnosis may be the reason for the excellent EFS in group A, B, C and D eyes. No significant financial relationships to disclose.