bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of ixabepilone (BMS 247550) in metastatic renal cell carcinoma
Authors: Posadas E. M. , Undevia S. , Colevas A. D. , Manchen E. , Vokes E. E. , Stadler W. M. 
Published: March 2020

14646 Introduction Ixabepilone (BMS) is a semi-synthetic analog of Epothilone B that functions as a microtubule stabilizer and has anti-cancer effects in several cancers including renal cell carcinoma (RCC) (Zhuang, ASCO 2004). The initial phase II study in RCC utilized a difficult and unconventional dosing schedule (6 mg/m2 IV days 1–5 every 21 days). Hence, this phase II study in RCC was designed to verify previous observations and to test the safety, feasibility, and activity of administering BMS once every 3 weeks- a schedule used in other malignancies. Methods Treatment consists of BMS 40 mg/m2 IV on day 1 every 3 weeks. Eligibility included metastatic RCC with clear or non-clear cell histology, no limits on the number of previous treatments, performance status 0–2, and normal organ function. The primary endpoint is the overall response rate by RECIST criteria on radiologic evaluation conducted every 9 weeks. Accrual to the full planned 41 patients (pts) will proceed provided that 2 or more responses are observed in the first 21 pts. Results Ten pts have enrolled (4 clear cell) with 1 declining participation prior to receiving any treatment. Eight pts have completed at least 3 cycles. Grade 3–4 toxicities include lymphopenia-2, diarrhea-2, alopecia-1, and infection-1. Grade 1–2 toxicities seen in more than 50% of pts include alopecia, neuropathy, nausea, fatigue, anemia, and lymphopenia. We have observed 1 unconfirmed partial response of short duration and 1 pt exhibited stable disease with a minor response but discontinued treatment due to excessive neurotoxicity. Three pts continue on treatment. Conclusions Toxicity at 40 mg/m2 IV on day 1 every 3 weeks is higher than previously reported with the daily x 5 schedule. While lymphopenia, diarrhea, neuropathy, and fatigue are all expected adverse events, the rates of toxicity across all grades is higher than previous reports. VHL mutation analysis is planned and will be correlated with response to therapy. Accrual and pt follow up continue. No significant financial relationships to disclose.
Prospective evaluation of a “Watchful Waiting” program using initial pathology criteria and PSA-doubling time monitoring for patients with stage T1c prostate cancer
Authors: Kakehi Y. , Kamoto T. , Ogawa O. , Tobisu K. , Saito Y. , Fukuda H. , Kakizoe T. 
Published: March 2020

14651 Background: “Watchful waiting (WW)” is becoming a common treatment option for patients (pts) with screening detected prostate cancer. There is, however, no consensus about which pts are suitable for WW and how pts are monitored. Methods: Eligibility criteria: 1) stage T1c prostate cancer pts, 2) age 50–80, 3) serum PSA: 20 ng/ml or less, 4) 1 or 2 positive cores per 6 to 12 systematic core biopsies, 5) Gleason score of 6 or less, 6) 50% or less maximum % cancer occupation in a positive core. The criteria of 4), 5), 6) were confirmed by a central pathologist before pts registration. Registered patients chose either WW or immediate aggressive treatment. In patients who chose WW, serum PSA was monitored every 2 months for 6 months and PSA-doubling time (PSADT) was calculated centrally. Those who showed PSADT 2y and re-biopsy at 13 months fit the initial pathology criteria again. Primary endpoint was “% PSADT > 2 y”, which was defined as proportion of patients who showed PSADT at 6 months > 2 y out of all patients who chose WW. Point estimate of “% PSADT > 2 y” was expected to be higher than 80%. The planned sample size was 100 pts who chose WW, which gives the width of 95% confidence intervals for % PSADT > 2 y within 10%. Results: 134 pts were enrolled from 01/2002 to 12/2003 and 118 pts chose WW while 13 pts chose aggressive treatment (surgery, radiotherapy, hormonal therapy). The initial 6 months’ PSADT could be assessed in 106 patients (measurement point error in 6, early dropout in 6). Of 106 patients, 22 showed PSADT < 2 y (“rapid riser”) while 84 showed PSADT > 2 y. “% PSADT > 2 y” was 71.2% (84/118, 95% CI: 62.1–79.2%). 84 pts have continued WW with median follow-up of 27 months. Neither metastasis nor cancer-death was observed until 06/2005. As to health-related QOL, any domain of SF-36 was not impaired in patients who continued WW at least for 1 year. Conclusion: Our initial selection criteria for WW may include at least 20% of “rapid riser”, hence need further modification. Additionally, it should be confirmed by further follow-up of 84 pts whether eliminating “rapid riser” from WW by initial 6 months’ PSADT is appropriate. No significant financial relationships to disclose.
Increased cytoplasmic localization of KLF5 in prostate cancer
Authors: Tsai H. T. , Datta M. , Frierson H. , Dong X. , Qiu Y. , Sun S. , Dong J. 
Published: March 2020

14652 Background: KLF undergoes genomic deletion, transcriptional downregulation, and excessive protein degradation in prostate cancer cells, but its protein expression has not been examined in prostate cancer specimens. Methods: We performed immunohistochemical staining on a tissue microarray composed of 37 benign prostate tissues, 58 primary prostate cancers, and 9 metastatic tumors. Cultured cells without KLF5 expression and those expressing KLF5 through gene transfection were used as controls. Each sample was scored for presence of staining, nuclear or cytoplasmic localization of staining, and intensity of staining (0, no staining; 1, below counterstain; 2, equal to counterstain; 3, strong staining obscuring counterstain). KLF5 expression was correlated with pathologic characteristics of tumors by performing Chi-square analysis and two tailed t tests. Results: KLF5 staining was noted in all 104 specimens, either as nuclear staining, cytoplasmic staining, or both. While no significant differences were seen in the intensity of the nuclear staining between benign and tumor groups, a significant increase in cytoplasmic staining was seen in tumor specimens (2.24 vs. 1.71, p = 0.0002). In addition, samples with high cytoplasmic and low nuclear KLF5 were more likely to be tumor samples (p = 0.0413). No significant differences were seen between samples with Gleason grades, or between primary tumors and metastases. Conclusions: Increased cytoplasmic localization of KLF5 may impair KLF5’s transcription factor function in the development and/or progression of prostate cancer. No significant financial relationships to disclose.
Late cardiovascular toxicity of BEP regimen among testicular cancer patients
Authors: Sadowska M. A. , Wiechno P. J. , Greszata L. , Paluchowska B. , Demkow T. 
Published: March 2020

14658 Background: Testicular cancer is the most common neoplasm in young men population. Standard chemotherapy for metastatic disease is BEP regimen (cisplatin, bleomycin, etopozyd). Evaluation of some late toxicities regarding cardiovascular system in patients with testicular cancer treated with orchidectomy and standard BEP regimen in comparison with patients treated with orchidectomy alone is presented. Methods: From February 2003 till July 2004, 153 patients (median age 37 year, range: 19–70) were enrolled into the study. The first group consisted of 93 men with metastatic testicular cancer, treated with orchidectomy and standard BEP regimen (3–10 courses, median 4). A control group consisted of 60 patients with stage I testicular cancer, after orchidectomy but without cytotoxic treatment. The patients who failed first line treatment or progressed were excluded from the study. Disease free survival was at least 2 years, median - 74 months (range: 24–327). Authors of the study created an inventory assessing cardiovascular risk factors, which was completed by every patient. Evaluation of the patient consisted of ECG, echocardiography, blood tests, assessment of the Body Mass Index and the risk of cardiac ischaemia incident according to the Polish Society of Cardiology guidelines. Results: Abnormal cardiac rhythm was more frequent among patients after chemotherapy then without cytotoxic treatment (24,8% and 6,7%, retrospectively, p = 0.004). There was also statistically important association between abnormal cardiac rhythm and the number of courses administered (p = 0.008). There were no statistically significant differences in conduction abnormalities (p = 0.218), echocardiography abnormalities (p = 0.72) and dimensions of the heart cavities (p = 0.26). Risk of cardiac ischaemia incident was similar in BEP and control groups (low risk 7.5% vs. 3,3%, moderate 26.9% vs. 16,7%, high 33.3% vs. 45% and very high 24.7% vs. 25%). There were no statistically significant differences between the two groups regarding abnormal BMI or lipidogram. Abnormal blood magnesium levels were more frequent among patients after chemotherapy (p = 0.009). Conclusions: Chemotherapy with BEP regimen increases the risk of rhythm abnormalities and the rate of abnormal blood magnesium level. No significant financial relationships to disclose.
Initial report of Radiation Therapy Oncology Group (RTOG) 9802: Prospective studies in adult low-grade glioma (LGG)
Authors: Shaw E. G. , Berkey B. , Coons S. W. , Brachman D. , Buckner J. C. , Stelzer K. J. , Barger G. R. , Brown P. D. , Gilbert M. R. , Mehta M. 
Published: March 2020

1500 Background: Treatment of adult LGG is controversial. Favorable patients (pts) (age <40 years [yrs] who undergo gross total resection [GTR]) are typically observed. Unfavorable pts (age ≥40 who have subtotal resection [STR] or biopsy [B]) are usually given initial radiation therapy (RT), reserving chemotherapy (historically procarbazine, CCNU and vincristine [PCV]) for recurrence. In 1998, the RTOG, in conjunction with SWOG, NCCTG, and ECOG initiated prospective studies of adult LGG, the results of which are reported herein. Methods: Favorable pts were observed postoperatively in a single arm Phase II study (Arm 1). Unfavorable pts were stratified by age, histology, KPS, and presence/absence of contrast enhancement on preoperative magnetic resonance imaging and randomized to either RT alone (54Gy in 30 fractions to a local treatment field) (Arm 2) or RT followed by 6 cycles of standard dose PCV (Arm 3). Reported results include overall survival (OS) rate, median overall survival time (MOST), progression-free survival (PFS) rate, and median progression-free survival time (MPFST). Survival data are compared using Wilcoxon p-values. Results: A total of 362 eligible/analyzable pts were accrued between 1998 and 2002. Median follow-up time is 4 years. For the 111 favorable pts observed on Arm 1, OS at 2- and 5-yrs is 99% and 94%. PFS at 2- and 5-yrs is 82% and 50%. For the 251 unfavorable pts on Arms 2 (RT alone) and 3 (RT+PCV), there was no difference in OS or PFS. OS at 2- and 5-yrs was 87% and 61% with RT alone versus (vs) 86% and 70% with RT+PCV (p=0.72). MOST was not reached in RT alone pts and was 6.0 yrs in RT+PCV pts. PFS at 2- and 5-yrs was 73% and 39% with RT alone vs 72% and 61% with RT+PCV (p=0.38). MPFST was 4.0 yrs with RT alone vs 6.0 yrs with RT+PCV. Acute grade 3–4 toxicity occurred in 9% of pts who received RT alone, 67% who received RT+PCV (mostly hematologic). There were no treatment deaths on either arm. Conclusions: 5-yr PFS was poor in all three arms ranging from 39% to 61%. Only half of favorable pts were disease-free at 5 yrs. In unfavorable pts, there was no OS advantage with the addition of PCV to RT. Both PFS and MPFST were better with the addition of PCV, but not significantly. Analysis of outcome by 1p19q status is pending. No significant financial relationships to disclose.
Small cell neuroendocrine carcinoma of uterine cervix: The Scottish experience
Authors: Siva M. , Mahmood R. , Kakumanu S. , Sadozye A. , Reed N. 
Published: March 2020

15026 Background: Small cell neuroendocrine carcinoma (SCC) of uterine cervix is a rare sub-type of cervical cancer. We report the results of a retrospective analysis of data from 2 Scottish centres of cases of SCC of cervix. The aim is to examine therapeutic interventions, relapse patterns and survival. Methods: Eligible cases were patients (pts) with cervical SCC presented for management discussion between 1995 and 2005 in the 2 scottish centres. Pathology was reviewed centrally by the network pathologists. We reviewed pts case records for staging information, therapeutic interventions, median time to relapse, salvage therapy and responses and overall survival. Results: A total of 21 pts were eligible for the analysis (Glasgow-13 and Aberdeen-8). The median age of the pts was 33 (Range 22–74). Nine pts were FIGO stage 1B, 3 were 2A and 4 were 2B, 3 were 3B and 2 with metastatic disease. Surgery was done in 13 pts [11-radical hysterectomy/pelvic lymphadenectomy, 1-radical hyseterctomy and 1-total abdominal hysterectomy]. Chemotherapy was given to 16 pts [Neo-adjuvant-6, Adjuvant-9, Concurrent-3]. Fourteen pts received combination chemotherapy containing Platinum and Etoposide [EP-2, CE-8, ICE-1 and ACE-3]. One received non-platinum combination. Fourteen pts received radiotherapy [10-Pelvic radiotherapy and brachytherapy, 3-Pelvic only, 1-Brachytherapy only, 2-PCI]. Two pts died of progressive disease shortly after diagnosis without any specific anti-cancer treatment, two pts were disease free after a follow up of 40 and 53 months respectively and one was lost to follow up 7 yrs after diagnosis. Median relapse free survival (RFS) was 16 months. Two year RFS was 25%. The sites of relapse were as follows: Liver-4, Chest-4, Para-aortic-4, Brain-3, Neck-3, Local-2, Abdomen-1. Twelve pts received salvage therapy after relapse [5-responded, 2-not assessed and 5-progressed]. Seven pts were alive after a median follow up of 40 months [Range 17–90]. Median survival was 28 months and the three year overall survival was 45%. Conclusions: We have shown here that with combination treatment SCC can be effectively managed with occasional durable remissions. The overall survival at 3 years was 45%. We believe this was the result of aggressive combination therapy of surgery, chemo and radiotherapy. No significant financial relationships to disclose.
High dose rate post-operative brachytherapy and external beam radiotherapy for uterine sarcomas
Authors: Maia M. A. , Novaes P. , Pellizzon A. C. , Ferrigno R. 
Published: March 2020

15027 Background: Uteine sarcoma (US) generally needs an aggressive approach with surgical cytoreduction at the time of initial diagnosis with maximum debulking of tumor. This offers the possibility of prolonged survival or cure. The need for adjuvant radiotherapy is not well established for US. Methods: 25 patients presenting completely ressected US were treated from November, 1992 to June, 2003. All the patients had a multidisciplinary approach with surgery, external beam radiation therapy (EBRT) given in a four- fields “box” technique, and high dose rate brachytherapy (HDRB), using either colpostats or vaginal cylinders with diameters ranging from 2.5 to 4 cm. The entire vaginal length treated with HDRB was 2 cm in all cases. Results: The median age of patients was 62 years (range 39–84). The EBRT dose prescription ranged from 40 Gy to 50,4 Gy (median 48 Gy). HDRB was given concurrent to EBRT in 14 patients (56%). The HDRB for the remaining patients started in median interval of 34 days (range 5–99 days) after the completion of EBRT. The median BED for hole treatment was 91.5 Gy10 (range 85.6 Gy10–97.9 Gy10), with a standard deviation of 3.7. The 10- year actuarial disease free and overall survivals were and 42.2% and 63.4%, respectively. On univariate analysis predictive factors for disease free survival (DFS) were age at initial presentation (p = 0.0268), parity (p = 0.0441), tumor grade (p = 0.0095), cervical or vaginal invasion (p = 0.0014) and node dissection at time of surgery (p = 0.0471). On multivariate analysis the only predictive factor was cervical or vaginal invasion (p = 0.048), hazard ratio of 4.7. Conclusion: Our small and heterogeneous group of patients analyzed precludes any definitive conclusions regarding the impact of HDRB combined to EBRT on recurrence or survival of the patients. As US are aggressive tumors, it is quite likely that neither radiotherapy nor chemotherapy alone will appreciably improve survival. If we assume that adjuvant radiation therapy provides better locoregional tumor control, hematogenous metastases probably will assume an even greater proportion of treatment failures. No significant financial relationships to disclose.
Pilot study of modafinil for treatment of neurobehavioral dysfunction and fatigue in adult patients with brain tumors
Authors: Kaleita T. A. , Wellisch D. K. , Graham C. A. , Steh B. , Nghiemphu P. , Ford J. M. , Lai A. , Peak S. , Cloughesy T. F. 
Published: March 2020

1503 Background: Patients with brain cancer develop neurobehavioral dysfunction and fatigue that compromise their performance of daily activities. We report results from evaluating the efficacy and safety of modafinil treatment for tumor/therapy sequelae in this medically fragile patient population. Methods: Patients: 21–65 years old with primary malignant disease or nonmalignant cerebral tumors treated with neurosurgical resection, radiotherapy, and/or chemotherapy. Clinical Global Impression of Severity ratings of mild to severe attention/memory impairment and/or fatigue. Measures: Trail Making (TM) A and B, Symbol Digit Modalities (SDM), Verbal Fluency (VF), Hamilton Depression Scale (HAM-D), Fatigue Severity Scale (FSS), Visual Analogue Fatigue Scale (VAFS), Modified Fatigue Impact Scale (MFIS). Design: Double-blind dose-controlled randomization (200 or 400 mg/day modafinil in divided doses) 3 wks; Washout 1wk; Open label extension 8 wks. Statistical analyses: Changes from baseline at scheduled visits (1, 3, 4, 8, 12 wks) using paired t-tests or Wilcoxon Signed Rank tests as appropriate. Results: Thirty patients, 63% male, mean age (SD) = 45.3 (11.7) yrs were accrued from 6/03–10/05. Illness severity: moderate 3 (10%), marked 13 (43%), severe 14 (47%). Tumor histology: glioblastoma multiforme 8 (27%), anaplastic glioma 10 (33%), low grade glioma 10 (33%), meningioma 1 (3%), CNS lymphoma 1 (3%). Treatment: neurosurgical resection 93%, radiotherapy 87%, chemotherapy 70%. The table shows relationships of nine variables at baseline and 8 and 12 weeks after initiation of modafinil. Adverse events reported by ≥4 patients: headache 13 (42%); insomnia 8 (26%); dizziness 7 (23%); dry mouth 7 (23%); depressed consciousness 5 (16%); nausea 4 (13%). Conclusions: Results show improvement across cognitive, mood, and fatigue outcome measures. Modafinil was generally well tolerated, with a low incidence of adverse events. Greatest improvements in outcomes were observed 8 wks after baseline. [Table: see text] [Table: see text]
A pilot study to assess the tolerability and efficacy of RAD-001 (everolimus) with gefitinib in patients with recurrent glioblastoma multiforme (GBM)
Authors: Nguyen T. D. , Lassman A. B. , Lis E. , Rosen N. , Shaffer D. R. , Scher H. I. , Deangelis L. M. , Abrey L. E. 
Published: March 2020

1507 Background: The majority of GBMs overexpress EGFR and have PTEN loss leading to activation of AKT signaling. mTOR is a downstream target which is blocked by RAD-001. The addition of an mTOR inhibitor to EGFR blockade by gefitinib may augment downregulation of AKT. Methods: Nineteen patients with GBM were enrolled in a phase I/II protocol open to patients with either hormone refractory prostate cancer or recurrent GBM. Patients on enzyme inducing anti-epileptic drugs (EIAEDs) were excluded, but prior treatment with an EGFR inhibitor was allowed. All patients received gefitinib 250 mg daily. Two patients enrolled in a dose escalation arm received RAD-001 30 mg or 50 mg weekly; 17 patients received the maximum tolerated dose of RAD-001 70 mg weekly. Baseline and follow-up MRIs were reviewed by a neuro-radiologist. Primary endpoints were radiographic response and progression-free survival (PFS). Results: There were 11 men and 8 women with a median age of 53 years (range 22–72) and median KPS of 80 (range 70–100). Seventeen patients (89%) were treated at their second or greater recurrence. The most frequent grade 1 and 2 toxicities were thrombocytopenia, elevated ALT, rash, anemia, leukopenia, and diarrhea. Grade 3 lymphopenia occurred in 8 patients (42%); two patients (11%) had grade 4 seizures unrelated to the study drugs. Five patients (26%) had a partial radiographic response, including one treated at 3rd recurrence, 2 treated at 4th recurrence, and one who had progressed through prior gefitinib therapy. Two additional patients (11%) had disease stabilization for greater than 4 months. Median PFS was 2.6 months. Median overall survival has not been reached, with a median follow up of 5.4 months for surviving patients. Conclusions: The combination of RAD-001 and gefitinib demonstrated activity in 37% of patients with GBM (26% responded, 11% achieved stable disease). Most subjects were heavily pre-treated and expected to have resistant disease. Because disease control was not durable, alternate dosing, or treatment earlier in the course of disease should be considered in further studying this promising combination. [Table: see text]
Immunological evaluation of personalized peptide vaccination for patients with malignant glioma: The results of a clinical phase I trial
Authors: Yamanaka R. , Yajima N. , Mine T. , Yamada A. , Shigemor M. , Ito K. 
Published: March 2020

1524 Purpose: To investigate the safety and immunological responses of personalized peptide vaccination in patients with malignant glioma. Patients and Methods: Twenty-six patients with recurrent malignant glioma entered in the phase I clinical study of personalized peptide vaccination. Peripheral blood mononuclear cells (PBMCs) and plasma prior to vaccination were provided for cellular and humoral responses in vitro to each of 31 or 36 peptides in cases of HLA-A24+ or HLA-A2+ patients, respectively, and then only the reactive peptides (maximum: 4) were allowed to in vivo administration. Post-vaccination PBMCs and plasma, and also pre-and post-vaccination cerebrospinal fluid, were provided for their reactivity to the vaccinated peptides. Expression of class 1 molecule on glioma cell was evaluated using EMR 8–5 antibody by immunohistochemical analysis. Results: The protocol was generally well tolerated, although the majority of patients developed grade 1 or 2 local redness and swelling at the injection site. Increase in cellular and humoral responses specific to at least one of the vaccinated peptides was observed in the post vaccination (6th)-PBMCs and -plasma from 62%, 73% respectively. More importantly, peptide-specific IgG were found in the post-vaccination cerebrospinal fluid of tumor sites. Clinical responses were 4 partial response, 8 stable disease, and 8 progressive disease. The clinical response was correlated to the expression of MHC class 1 on the glioma cell. The median overall survival for patients with recurrent glioblastoma multiforme in this study was 622 days. Conclusion: Personalized peptide vaccination is well tolerated and has ability to induce immune responses to the majority of malignant glioma patients along with several cases of major tumor regression. These results would encourage the phase II clinical study of personalized peptide vaccination to patients with recurrent malignant glioma. No significant financial relationships to disclose.