bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant paclitaxel plus carboplatin followed by concomitant radiochemotherapy in stage IVb nasopharyngeal carcinoma: Preliminary results
Authors: Jouhadi H. , Tawfiq N. , Sahraoui S. , Benider A. 
Published: March 2020

15521 Background: Nasopharyngeal cancer Is the first head and neck cancer in Morocco. undifferentiated carcinoma (WHO 3)is dominant. Loco regional advanced stages IVa and IVb (AJCC/UICC 1997) represents 60 to 78%. Classical treatment is neoadjuvant chemotherapy (3 courses of BEP protocol) followed by radiotherapy. Therapeutic results are characterised by a high rate of failure. For stage IVb failure is due to distant metastasis wich occur in 30 to 40% of cases needing more systemic therapy. The aim of this prospective study is to analyse for stage IVb the benefit of introducing paclitaxel associated to carboplatin as a neoadjuvante chemotherapy followed by chemoradiation in terms of reducing distant metastasis and improving local control. Tolerance of this protocol was also analysed. Methods: Between September 2003 and January 2004, a total of 33 previously untreated, histologically confirmed NPC adults, were enrolled in this study. The new protocol is based on 1-Four courses of neoadjuvant chemotherapy (1 course = paclitaxel: 175 mg/m2 day 1 + carboplatin: 300 mg/m2 day 1; 1 course every 21 days) 2-followed by a concomitant radiochemotherapy: -radiotherapy to a total dose of 65 gray -and low dose of cisplatine (30 mg/m2) delivered on a weekly schedule. Eligibility criteria were: histologically confirmed NPC, stage IVb, no prior treatment, and informed consent of patients. There were 21 male and 12 female patients and their ages ranged from 19 to 58 years. Results: The minimal follow up was 2 years. The 2 year DFS was 85% and the 2 year loco regional free survival was 91%. All patients completed radiotherapy. Neutropenia grade III-IV was observed in 6% without fever. According to NCI toxicity criteria, acute mucositis (due to radiation) grade 3 was observed in 15% and grade 2 in 24%. Xerostomia grade 1 was observed in 70%. Conclusion: This protocol is very effective with less toxicity. Radiation dose is reduced without decreasing local control rate. The 2 years DFS is increased with this protocol to 85%. No significant financial relationships to disclose.
Nutritional and environmental risk factors of nasopharyngeal carcinoma in Morocco
Authors: Bouras N. , Tahri A. , Ammor S. , Baali A. , Tahiri F. 
Published: March 2020

15535 Background: The nasopharyngeal carcinoma (NPC) has a high incidence in north Africa and in southeast Asia. The goal of this study is to analyze the implication of nutritional and environmental factors in the raise of this cancer. Methods: It is a retrospective investigation with 274 affected by the NPC and 394 witnesses. Results: The nasopharyngeal carcinoma affects mens more then womens with a sex ratio of 1.8. We observed a peak between 20 and 29 years with the women and between 40 and 49 years with the men. We noted also a high frequency of the young population touched by this disease: 10.5% less than 20 years old, which was also observed in Tunisia, Algeria and Sudan while the young patients are rarerly affected in the Asian southeast. The patients have mostly rural origin with agricultural parents, having lived during their childhood in precarious habitat and hygiene conditions and with an instruction level generally low, often without function or exercising in the primary or secondary sector. The study of nutritional and environmental risk factors showed a statistically meaningful relation between this cancer and some factors bound to the food: consumption of pickle, of smen (butter fermented), and to the environment: life in agricultural environment, practice of the farm, absence of drinkable water and contact with toxic substances. Conclusions: It seems that the exposition to environmental risk factors could increase the risk to contract this cancer, especially with the already exposed persons to nutritional risk factors. We observed a territorial variability of the exposition to the NPC risk factors that explains the gradient south north of the incidence of this cancer in Morocco. The results of this study show the complexity of factors being able to take to a cancerogenesis. No significant financial relationships to disclose.
Safety and tolerance of multiple weekly intracavitary injections of 131I-chlorotoxin (TM-601): Preliminary results of a prospective clinical trial in patients with recurrent glioblastoma multiforme
Authors: Fiveash J. B. , Nabors L. B. , Mamelak A. N. , Avgeropoulos N. G. , Guthrie B. L. , Salomon N. W. , Portnow J. , Bucholz R. D. 
Published: March 2020

1555 Background: 131I-chlorotoxin is a peptide originally derived from scorpion venom that will specifically bind to tumor cells targeting lamellipodia and produces a variety of secondary messenger effects through phosphatidyl inositol signaling. Preclinical studies suggest it is both a radiation and chemotherapy sensitizer. A previous phase I/II clinical trial defined the distribution and dosimetry of single injection intracavitary 131I-chlorotoxin and suggested clinical activity in patients with recurrent glioma. Methods: 15 patients with recurrent GBM after prior treatment (radiation therapy), were enrolled in this sequential, multiple-dose escalation study with re-resection and implantation of a ventricular access device (VAD) into the resection cavity. Dose limiting toxicity was defined as any grade 3 or greater toxicity judged probably related to study drug and occurring within 7–11 days of the last dose. Dosing cohorts of 3–5 patients were entered at each of the listed dose levels designed to maintain a constant drug specific activity. Results: One subject did not complete treatment due to thrombocytopenia possibly related to a VAD infection necessitating removal of the VAD following the initial dose of study drug. Eight serious adverse events (SAEs) were observed in 15 patients after study drug administration. These included seizure, cerebral edema, and gait disturbances. None were judged to be both unexpected and related to study drug. No dose limiting toxicity was observed. Two subjects experienced Grade 1/2 CTC 3.0 neutropenia. Conclusions: The safety profile of weekly intracavitary injections of 131I-chlorotoxin was acceptable. Dose limiting toxicity was not reached at the final planned dose level D (6 x 40 mCi/0.8 mg peptide, total 240 mCi), which is the maximum practical dose. Accrual to the randomized phase II portion of this trial comparing three vs. six weekly injections began 12/2005. [Table: see text] [Table: see text]
A stratified phase II study of cetuximab for the treatment of recurrent glioblastoma multiforme: Preliminary results
Authors: Sadones J. , Chaskis C. , Joosens E. J. , Dhondt L. A. , Baurain J. , In ’t Veld P. , Michotte A. , De Grève J. , Neyns B. 
Published: March 2020

1558 Background: The Epidermal Growth Factor Receptor (EGFR) gene is frequently amplified and mutated in high-grade gliomas. We are investigating the activity of the EGFR-targeted monoclonal antibody cetuximab for the treatment of patients (pts) with recurrent glioblastoma multiforme (GBM) following surgery, radiotherapy and chemotherapy. Methods: Adult pts with recurrent GBM are allocated to two parallel treatment strata according to the amplification status of the EGFR gene (determined by FISH). According to a Simon two-stage phase II study design 1 response in 13 pts/stratum is required to continue recruitment and complete the second stage of pt recruitment. Cetuximab is administered at 400 mg/m2 (2 hour infusion) day 1 and 250 mg/m2 day 8 and for all subsequent weekly doses (1 hour infusion). Results: Between May and December 2005, 17 pts were recruited (10 without EGFR-ampl, 4 with EGFR-ampl and 3 under investigation); 4F/13M; median age 51 years, range 32–67). Recruitment is ongoing. Sixteen pts initiated study treatment; 1 pt withdrew consent before the initiation of therapy. Treatment related toxicity in the first 94 treatment cycles consisted of grade 1/2 folliculitis/dermitis in all treated pts. Grade 3 adverse events consisted of thrombocytopenia (n=1 pt), diminished consciousness (n=1 pt), dizziness/confusion (n=1 pt), infectious bronchopneumonia (n=1 pt), and infectious cellulitis (n=1 pt). Thirteen pts have been evaluated for response ≤ week 8 of study treatment. Eleven pts had progression of disease. Two patients had SD at 8 weeks (follow-up is ongoing). Conclusions: These preliminary data suggest that cetuximab can be safely administered to pretreated patients with recurrent GBM. Updated results regarding safety and activity as well as a correlative study of EGFR and PTEN expression and gene copy number of the GBM and response to cetuximab will be presented at the meeting. No significant financial relationships to disclose.
Protracted administration of low doses of temozolomide (TMZ) in the treatment of relapse glioblastoma (GBM) enhances the antitumor activity of this agent
Authors: D’Amico A. , Gabbani M. , Dall’oglio S. , Cristofori L. , Turazzi S. , Sanzone E. , Maluta S. 
Published: March 2020

1572 Background: The efficacy of temozolomide (TMZ) is strictly related to the possibility to reach and maintain high and prolonged cellular drug concentrations in the target tissue. Evidence exists demonstrating that the achievement of this goal and the subsequent activity of TMZ are categorically schedule dependent. Aim of the present randomized phase II study is to verify whether a treatment schedule with TMZ appropriately modified induces better response rates along with a decrease of mielotoxicity as compared to the conventional one. Methods: Twenty patients (5 F/15 M), median age of 53 years (range 35–74), median Karnofsky PS 90 (range 70–100), with GBM in progression after surgery and adjuvant RT have been treated as follows: Schedule A - TMZ for 5 days in a 28-day cycle, at the dose of 150 mg/m2/d at the first cycle and of 200 mg/m2/d thereafter, up to a total of 8 cycles. Schedule B - TMZ for 7 days alternating with 7 days of rest up to a total of 12 cycles: the starting dose of TMZ at the first cycle was 50 mg/m2/d with progressive serial dose escalations of 25 mg/m2/d in the subsequent ones until the achievement of the dose of 150 mg/m2/d at the 5th cycle, and then keeping this regimen until the 12th cycle. Results: They are summarized in the table : Severe thrombocytopenia and stomatitis have been observed only in patients treated with Schedule A. Conclusions: These preliminary results, which deserve to be confirmed in a larger sample size, indicate that the treatment with TMZ on alternate week basis is strongly interesting and promising. In spite of the modality and the small number of patients included in this study, which doesn’t allow a direct comparison between two different treatments, it should be noted that schedule B achieved a 2-year OS and PFS rate of 40% and 20% respectively, compared to 10% and 0% of schedule A. [Table: see text] No significant financial relationships to disclose.
MGMT expression correlates with response rate and survival in patients with inoperable glioblastoma (GBM) treated with neoadjuvant temozolomide (TMZ)
Authors: Barrie M. , Eudes N. , Metellus P. , Fuentes S. , Honore S. , Boucard C. , Dufour H. , Figarella-Branger D. , Chinot O. 
Published: March 2020

1574 Background: Methylation of the promotor of O6-alkylguanine alkyltransferase (MGMT), a DNA repair gene, may enhance chemosensitivity to alkylating agents. In GBM, this methylation has been correlated to survival as well as to the benefit of adding TMZ concomitant and adjuvant to radiotherapy (RT) (Hegi, NEJM, 2005). We examine the relationship between MGMT expression and objective response rate to dose intense TMZ schedule administered as neoadjuvant treatment before RT in inoperable GBM, as previously presented (Chinot, ASCO, 2005). Methods: Thirty patients were included in this phase II trial that tested TMZ (150 mg/m2/day) on days 1 to 7 and 15 to 21 of each 28 days cycle for up to 4 cycles prior to RT. We analysed retrospectively MGMT expression by immunochemistry (streptavidin-peroxydase) after antigen retrieval using anti-MGMT antibody (Abcys, 1/100) in 25 formalin-fixed paraffin embedded samples from the study population. Results: In the eligible population (n = 28) response rates (RR) were of 25% (95% CI, 8.63% to 41.37%); SD 32%; PD 43%. Median progression free survival (PFS) and overall survival (OS) were 3.8 and 5.8 months, respectively. MGMT expression was analysed in 25 pts while material was considered as inadequate in 3 pts because of insufficient tumor material. The median percentage of cells that expressed MGMT in tumor nuclei was 35% and so was chosen as cut-off. Low MGMT expression was significantly associated with a high RR (55%) while tumor that exhibit high MGMT expression was associated to a RR of 9% (chi-2 p=0.004). MGMT was also strongly correlated to PFS (log rank p=0.009) and OS (log rank p=0.003). Conclusion: Despite limited number of patients, our study strongly supports the predictive value of MGMT expression for objective response to TMZ in addition to its prognostic value for PFS and OS in GBM. If confirmed in prospective study, MGMT expression may help to guide therapeutic decisions as well as more targeted trial design. [Table: see text] No significant financial relationships to disclose.
Prolonged gemcitabine infusion as radiosensitizer for newly diagnosed glioblastoma multiforme (GBM): A phase I study
Authors: Carapella C. M. , Mirri A. M. , Felici A. , Vidiri A. , Pace A. , Carosi M. A. , Occhipinti E. M. , Arcangeli G. , Cognetti F. , Fabi A. 
Published: March 2020

1581 Background: The use of cytotoxic drugs concurrent with RT represents a promising approach in the combined treatment of malignant gliomas. Gemcitabine (dFdCyd) is a drug widely explored for its potential radiomimetic activity in different tumors. The present study was aimed to evaluate the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of weekly prolonged dFdCyd infusion, administered in combination with RT as first line treatment, in adult pts affected by supratentorial GBM. Methods: Within 6 weeks after surgery, in the presence of measurable residual disease and KPS >70, pts were treated with fractionated RT at a dose of 2.0 Gy/daily fractions, 5 days a week (global dose 60 Gy). From 24 to 72 hours before the first RT application, and afterwards once weekly, pts received concurrent dFdCyd, at fixed dose rate of 10 mg/m2/min, over a total period of six weeks. Planned dose levels of dFdCyd started from 200 mg/m2/weekly (level 1), with sequential steps of 25 mg/m2/w based on toxicity. Results: Ten pts were enrolled into the study: six were male, median age 55.2 years (range 44–75), with a median KPS at baseline of 85 (SD 9.71). The median time from diagnosis to the start of treatment was six weeks (range 4–7). The median RT duration was 6 weeks (range 4–7), all but one pt received the planned dose and all pts received concomitant CT. Four pts entered at Level 1; one pt was excluded from the study, due to rapid progressive disease during the treatment. Two of the three valuable pts presented a relevant neurological worsening; on this basis the dFdCyd dose was reduced to 175 mg/m2/w (Level -1). A total of six pts were entered at Level -1, and none of them reported DLT. No hematological grade 3–4 toxicity was reported. Grade 3 non-hematological toxicity was observed in one pt (transaminases increase). After a median follow-up of 13.4 months (range 3–24), the median progression-free survival was 8 months (CI 95% 1–18), and the median overall survival was 14 months (CI 95% 12–17). Conclusions: The recommended dose of prolonged infusion of dFdCyd concomitant with RT is 175 mg/m2/w. The observed activity has been considered interesting enough to support a phase II study of this concurrent CT-RT schedule as first line treatment in GBM. [Table: see text]
The ERB family receptor dimerization in glioblastoma—An eTag assay analysis of 23 cases
Authors: Hameed M. R. , Sharer L. , Cho E. , Aisner S. , Cao L. , Tan Y. , Mukherjee A. , Chenna A. , Singh S. , Petropoulos C. 
Published: March 2020

1582 Background: Glioblastoma is the most malignant astrocytic tumor and accounts for about 50–60% of all astrocytic neoplasms. Despite intensive radiation and chemotherapy, less than 2% of patients survive more than 3 years. The Erb family of signaling molecules are transmembrane receptors with intrinsic kinase activity (except ErbB3) capable of modifying tyrosine residues on the receptor itself as well as on downstream signaling molecules. Under physiological conditions a variety of ligands interact and act as driving forces in the formation of homo and heterodimeric complexes between the four receptors leading to signal amplification and downstream activities. More than one third of glioblastoma cases show gene amplification of epidermal growth factor receptor (EGFR) which can be in truncated or rearranged form. The eTag assay system (Monogram) is an antibody based fluorescent assay that has the potential to assess the activation state of the EGFR signaling pathway. Methods: Twenty three cases of glioblastoma were selected for eTag analysis. There were twelve males and eleven females with ages ranging from 20–84 years. After reviewing the histology, 10 micron sections were cut from formalin fixed paraffin embedded (FFPE) tumor tissue blocks. Specific monoclonal antibodies of the Erb family bound to a fluorescent reporter (eTag) were applied to tissue sections. After binding of specific analyte, a second monoclonal antibody is added which acts as molecular scissors resulting in cleavage of “eTags”. The released eTag molecules are separated by capillary electrophoresis and measured as relative fluorescent units. Various FFPE tumor cell lines were used as controls. Results: Nineteen out of twenty three tumors (82%) showed the presence of dimers of the Erb family signaling pathway. High levels of intra and /or extracellular EGFR homodimers (HER-1-HER-1) were detected in eight samples (35%). EGFR-HER-3 dimers and EGFR-HER-2 dimers were seen at high levels in four and six samples (17% and 26% respectively). High levels of HER-2-HER3 dimers were detected in six samples (26%). Conclusion: The EGFR signaling pathway plays a substantial role in tumorigenesis of glioblastoma. Identification of receptor homo and heterodimers may be of value during treatment planning of individual patients. No significant financial relationships to disclose.
Palliative chemotherapy preferences and factors that influence patient choice in advanced cancer
Authors: Kim M. , Lee K. , Hyun M. , Do Y. , Song H. , Kim J. , Baek J. , Bae S. , Ryoo H. , Park K. 
Published: March 2020

16010 Background: We conducted this prospective study to determine the treatment preference of patients receiving chemotherapy in a palliative setting. We investigated the survival threshold for justifying toxicity, the factors influencing individual preference for chemotherapy, and the attitude of patients towards randomized trials. Methods: 138 patients (median age, 58 years; 73% male) with advanced cancer who had received at least one cycle of palliative chemotherapy were recruited. General demographic information, patient preferences for palliative chemotherapy, and randomized trials were determined using structured patient interviews. Results: The median age was 58 years (range, 25–77 years), and the majority of the study population were male (73%). 73 patients (60.1%) answered that they had some support by dependents. Fewer than half were given information about the impact of their chemotherapy on survival (n = 64, 48.1%), and just over one third of patients (n = 53, 40.5%) were presented with an alternative to anticancer therapy, such as supportive care (p < 0.001). While 75.7% of patients agreed to receive chemotherapy with mild toxicity, only 57.9% of patients agreed to chemotherapy with severe toxicity (p = 0.002). The median survival threshold was 12 months for mild toxicity, and 21 months for severe toxicity. Patients who experienced improvement of symptoms or quality of life were more likely to judge the treatment as acceptable. 105 patients (78.4%) refused a clinical trial with randomization between a conventional chemotherapy and supportive care. There were 85 patients (62.6%) that would refuse randomization between conventional chemotherapy and investigational chemotherapy. Finally, 58.6% of patients agreed to participate in trials with investigational agents. Conclusions: In the palliative setting, a discussion of prognosis and the merits of chemotherapy is a necessary part of the treatment decision-making processes, and choosing the proper treatment for cancer patients. Individual preferences assume greater importance in this setting. Randomized trials must be carefully designed with a priori equipoise. No significant financial relationships to disclose.
A comparison of hematology/oncology clinic attendance between insured and under-insured patients at an urban academic hospital: Identifying barriers and ways to overcome them
Authors: Youssef J. A. , Lyckholm L. J. , Smith T. J. , Shickle L. M. , Matsuyama R. K. , Parker G. L. 
Published: March 2020

16015 Background: There are persistent disparities in cancer outcomes based on non-clinical factors such as race, socioeconomic status, and access to care. Successful treatment outcomes in oncology and symptom control depend heavily on patient compliance. To improve patient attendance at oncology appointments, the reasons why patients miss appointments must be understood, and then interventions must be enacted to rectify the problem. Methods: At the hematology/oncology clinics of Virginia Commonwealth University, the fellows’ clinic consists of patients that are primarily uninsured or underinsured, and the faculty clinic consists of patients that are primarily well-insured. On Mondays and Fridays from January 31–June 30, 2005, attendance of scheduled patients was recorded. Patients were then called and asked why they did not attend their appointments. Also, the patient’s sex, age, race, diagnosis, and insurance status were recorded. Results: Of the 1705 appointments scheduled in the predominantly under-insured fellows’ clinic, 223 (13.1%) of these were no shows. Of the 1614 appointments scheduled in the better-insured faculty clinic, 115 (7.1%) of these were no-shows (p < .0001). Of African-American patients in both clinics, 30.9% did not attend their appointments as compared to 19.4% of Caucasian patients (p = .0003). The no-show rate among women was 22.4% as compared to 28.6% for men in both clinics (p = .025). Of all patients under age 50, 30.1% did not show up as compared with 22.4% of all patients aged 50 or higher (p = .009). Chi-square was used to test for significance. Among both clinics, the reasons for missing appointments included: the patient did not know of the appointment (35), patient illness (24), transportation difficulties (12), family emergency (7), forgot (7), and weather (2). Conclusions: In this study, appointment knowledge and patient illness affect oncology clinic attendance most. It is our goal to implement measures, such as appointment reminders and transportation assistance, and then reassess attendance rates. No significant financial relationships to disclose.