bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anaemia in patients with transitional cell carcinoma (TCC) of the bladder treated with radiotherapy
Authors: Joynson C. , Symonds P. , Sundar S. 
Published: March 2020

14569 Background: Treatment of muscle invasive TCC of the bladder with radiotherapy allows organ preservation and is frequently used in the UK especially in patients not medically fit for cystectomy. Anaemia is known to be an indicator of poor response to radiotherapy in head and neck and cervical carcinomas. This study describes the prevalence and type of anaemia in patients with TCC of the bladder and looks at the impact anaemia has on treatment outcome. Methods: Retrospective review of notes was performed on patients treated radically between 1992 and1997. Potential patient, tumour and treatment prognostic indicators were reported. Patients were labelled as being anaemic if their pre treatment haemoglobin level was below the normal range (below 13.5g/dl for men and below 11.5g/dl for women). Time to local recurrence, metastases and overall survival was recorded. Recurrence free survival and overall survival actuarial estimations were done using the Kaplan Meier method and compared by log rank testing. Multivariate analysis was carried out using Cox Regression method, correcting for potential confounding factors. Results: Data on 100 patients were available for analysis. 52 patients were anaemic with 75% of these having a normochromic, normocytic anaemia. Univariate analysis showed no significant difference in time to local recurrence, a trend to shorter time to metastases, and a significant reduction in overall survival in anaemic patients (p = 0.04). Two year survival was 43% and 22% for non anaemic and anaemic patients respectively. Multivariate analysis using covariates tumour stage, grade, and serum creatinine found anaemia to be poor prognostic indicator for overall survival (p = 0.005) and time to metastases (p = 0.003). Conclusions: Anaemia is highly prevalent in patients with bladder cancer. This retrospective study shows anaemic patients to have a worse outcome with radiotherapy treatment than patients with a normal haemoglobin level. This is not accounted for by a difference in local control which may be expected from hypoxic radiobiological principles. Anaemia may be indicative of more aggressive malignancy or sub clinical metastases. No significant financial relationships to disclose.
Adjuvant thalidomide improves disease specific survival for patients with renal cell carcinoma at high risk for relapse following surgery
Authors: Sanchez-Ortiz R. , Tamboli P. , Lozano M. L. , Matin S. , Wood C. G. 
Published: March 2020

14586 Background: Observation is the standard of care for locally advanced renal cell carcinoma (RCC) after surgery. No adjuvant therapy for RCC exists. Thalidomide has shown activity in metastatic RCC. We studied thalidomide in the adjuvant setting for patients with locally advanced RCC. Methods: This phase III trial has enrolled 46 patients to date. All patients underwent resection of all disease. Eligible patients included T2N0M0 grade 3–4, T3a-cN0M0, T4N0M0, TanyN1–2M0, and TanyN0M0 bilateral disease completely resected. All RCC histologies were included. Patients were randomized to observation or thalidomide, 300 mg daily for 2 years. Dose reductions were allowed for toxicity. The primary endpoint was recurrence free survival. Secondary endpoints were disease specific survival and toxicity. Results: Twenty-three patients randomized to thalidomide and 23 were observed. In the thalidomide arm, one patient refused therapy and two stopped within one month due to toxicity. Only 1 patient tolerated therapy for 2 years without dose reduction. With a median follow-up of 18 months, there were 6 recurrences and 5 disease related deaths in the observation arm and 7 recurrences and 2 disease related deaths in the thalidomide arm. Using an intent to treat principle in our multivariate analysis, adjusting for grade, stage, and nodal status, we noted no significant difference in recurrence free survival between observation (mean 31 months; median not reached (NR)) and the thalidomide arm (mean 24.7 months; median NR) (Hazard ratio = 1.04, 95% CI 0.34 to 3.14, p = 0.945). Interestingly, disease specific survival was significantly better in the thalidomide arm (mean 40.1 months; median NR), as compared to the observation arm (mean 37.1 months; median NR) (Hazard ratio = 0.086, 95% CI 0.008 to 0.981, p = 0.048). Conclusions: In this limited experience with surgically resected RCC at high risk for relapse, thalidomide did not impact time to recurrence but significantly improved disease specific survival in the adjuvant setting. Despite this clinical benefit, significant toxicity limited tolerability of the drug. These data suggest that derivatives of thalidomide, with different toxicity profiles, might warrant testing in the adjuvant setting for RCC. No significant financial relationships to disclose.
Hemochromatosis gene (HFE) mutations and chemotherapy-related cardiovascular risk profile in testicular cancer survivors (TCS)
Authors: De Haas E. C. , Meijer C. , Zwart N. , Van der Steege G. , Boezen H. M. , Sleijfer S. , Van Leeuwen F. E. , Smit A. J. , Sleijfer D. T. , Gietema J. A. 
Published: March 2020

14589 Background: TCS show an increased incidence of treatment-related cardiovascular disease. Standard chemotherapy (CT) may cause tissue damage by inducing free oxygen radicals through release of redox-active iron from body iron stores. HFE mutations associated with altered body iron load may therefore contribute to an increase in CT-induced free oxygen radicals and tissue damage. We investigated whether two HFE mutations (C282Y and H63D) are associated with cardiovascular risk profile in TCS. Methods: From a group of 90 TCS with a known cardiovascular status (JCO 2005; 23: 3718–25), genomic DNA for genotyping was available for 63 TCS (median (range) age at follow-up 35 y (24–54) and median follow-up duration 7 y (3–13)). Two HFE genotype groups were composed: HFE mutation (mut) (n = 19; any mutation C282Y and/or H63D) and HFE wild type (wt) (n = 44). Both groups were compared for cardiovascular risk profile, using Mann-Whitney U Test or Fisher’s Exact Test. Results: Groups had received comparable CT regimens. Body iron stores as reflected by plasma ferritin and transferrin saturation were not different for the HFE mut vs HFE wt group, respectively 104 μg/l (21–413) vs. 90 μg/l (22–569); p = 0.53 and 31% (20–49) vs. 30% (11–59); p = 0.15. Signs of vascular damage estimated by urinary albumin excretion and Von Willebrand factor levels were not significantly different: respectively 8.3 mg/24 h (4–165) vs. 7.7 mg/24 h (3–647); p = 0.90 and 90% (52–296) vs. 102% (28–235); p = 0.25. The prevalence of cardiovascular risk factors obesity (BMI > 27.8 kg/m2), metabolic syndrome (NCEP ATP III-criteria) and hypertension (mean 24-h blood pressure >135/85 mmHg) are shown in the table. Conclusion: TCS with a mutation in the HFE gene do not show more signs of cardiovascular damage after CT compared to TCS with wt HFE. However, the data suggest that TCS with a HFE mutation may have more frequently cardiovascular risk factors. Further study in a larger group of TCS is needed to explore this observation. [Table: see text] No significant financial relationships to disclose.
The influence of body mass index (BMI) on outcome in patients with advanced germ cell tumors (GCT)
Authors: Vaughn D. J. , Powell M. , Catalano P. J. , Loehrer P. , Nichols C. , Sweeney C. , Wilding G. , Dipaola R. S. 
Published: March 2020

14594 Background: Obesity is associated with increased mortality in a variety of cancers. Using data from ECOG 3887, a phase III study comparing cisplatin, etoposide, and bleomycin or ifosfamide in advanced GCT, we explored the prognostic significance of BMI. Methods: From 10/87 to 4/92, 286 assessable patients (pts) were enrolled in the original study. 1 pt was ineligible, 3 pts were missing weight/height; 282 pts are included in this analysis. BMI was computed by dividing weight by square of height (kg/m2), and was categorized as underweight (< 18.5), normal (18.5–24.9), overweight (25–29.9) and obese (>30). A favorable response was defined as CR, NED post-surgery, or PR for ≥ 2 years. Fisher’s Exact Test was used to examine associations between BMI and favorable response. The Kaplan-Meier method was used to estimate overall survival by BMI. Proportional hazards models were used to examine the effect of BMI on survival after adjusting for International Stage (IS) and performance status (PS). As BMI was distributed similarly between the two treatment arms and no treatment differences were observed in the primary analysis, data from both arms were pooled to maximize power with regard to BMI. Results: Fifteen pts (5%) were underweight, 171 (61%) normal, 75 (27%) overweight, and 21 (7%) obese at study entry. The favorable response proportion was 53%, 67%, 51%, and 65%, respectively, for underweight, normal, overweight and obese pts. There was no association between BMI category and favorable response probability (chi square p = 0.08). 5-year survival for underweight, normal, overweight, and obese pts was 60%, 73%, 62%, and 67%, respectively. There was no difference in overall survival associated with BMI category (logrank p = 0.28), although statistical power is limited since there were few underweight/obese pts. After adjusting for IS and PS, there remained no association between overall survival and BMI category (hazard ratio per unit BMI 1.01, 95% CI 0.97–1.06). Conclusions: We observed no association between BMI and outcome, but statistical power is limited due to the small number of underweight and obese pts. No significant financial relationships to disclose.
Summary of results in patients with metastatic renal cell cancer (RCC) from phase I studies of RAD001 (everolimus)
Authors: Porter L. L. , Burris H. A. , Jones S. F. , Calvert S. , Papadimitrakopoulou V. A. , Hazell K. , Shand N. , Lebwohl D. , Baselga J. , Judson I. 
Published: March 2020

14599 Background: Activation of mammalian target of rapamycin (mTOR) is implicated in the pathogenesis of RCC. Hereditary RCC in tuberous sclerosis pts is associated with loss of function of TS complex genes and resultant activation of mTOR. In non-hereditary RCC, mutation of VHL reduces opposition to mTOR-dependant upregulation of HIF. HIF-1α stimulates growth-factor-mediated activities (VEGF, PDGF, TGFα) supporting tumor-growth and proliferation. RAD001, an orally bioavailable inhibitor of mTOR, could have a role in the treatment of pts with RCC. Methods: All pts with metastatic RCC treated in two phase 1 studies of RAD001 in advanced solid cancer were reviewed. Changes in tumor were assessed using RECIST. Results: There were 12 pts (8.2% of total study population) with histology of clear cell (10 pts), papillary (1 pt), sarcomatoid (1 pt). Dosing was either weekly (20 mg:1 pt, 50 mg:2 pts, 70 mg:4 pts) or daily (10 mg:5 pts). 8 pts were male, 4 female. Median age 60 yrs (range: 44–76). Baseline performance status (WHO) was 0 (2 pts) or 1 (10 pts). Metastatic sites included lung (9 pts), bone (7 pts), liver (2 pts). 10 pts had failed prior drug therapy including IL-2 (2 pts), bevacizumab & erlotinib (7 pts), others (5 pts). Most frequent suspected drug reactions (3 pts or more) were: fatigue, diarrhea, rash, anorexia, mucositis, nausea, abdominal distension, vomiting, headache. Gr.3 events in single pts comprised: hypertriglyceridemia, hyperglycemia, epistaxis with prolonged bleeding time. 6 pts were progression-free at 6 months, 4 pts beyond 12 months (max. 20 months ongoing). Partial response apparent in 1 pt (papillary) on D334 is ongoing at D502. Conclusions: Advanced RCC pts can benefit from RAD001 as indicated by prolonged stable disease in half the cohort. Tumor shrinkaqe may appear only after several months of treatment. Toxicity is mostly mild and similar to patients with other tumor types. Further studies of RAD001 in pts with RCC are planned. [Table: see text]
A phase I study of LR-103 (1,24α(OH)2D2) in patients with refractory malignancies
Authors: Bailey H. , Kolesar J. , Fass T. , Weiss J. , Heideman J. , Alberti D. , Morgan-Meadow S. 
Published: March 2020

14608 Background: Preclinical studies of calcitriol and vitamin D analogs demonstrate potent growth inhibition of tumor cell lines. The clinical development of calcitriol and other analogs have been hindered by hypercalcemia. 1α (OH)D2 is a Vitamin D analog which has produced objective responses in advanced androgen-independent prostate cancer patients and can be administered daily at 10mcg. LR103 is an active metabolite of 1α (OH)D2 with equivalent anti-tumor activity and significantly less calcemic effects in preclinical studies. This phase I study explores the maximal tolerated dose and toxicity of LR-103. Methods: LR-103 was administered daily beginning at a dose of 5 μg/day with a cycle length of 14 to 28 days. Dose escalation proceeded in two stages. In step A, intra-patient dose escalation (starting dose of 5mcg daily) was allowed based on degree of toxicity regardless of attribution. Step A escalation continued until 2 patients had ≥ grade 2 toxicity at a dose level. Step B is a standard, inter-patient only, dose-escalation trial (starting dose based on Step A) with cohorts of three. Dose limiting toxicity is defined as ≥ grade 3 toxicity. Results: Nineteen patients have enrolled between May and December 2005, eight to step A and eleven to step B. During step A escalation, two patients at 15 μg/day experienced severe toxicity (grade 4 hyperuricemia and grade 3 alkaline phosphatase) and two patients at 15 μg/day experienced grade 1 hypercalcemia. Hypercalciuria has been common. No hypercalcemia ≥ grade 2 has been observed. Step B enrollment continues at 30 μg/day without hypercalcemia. Conclusions: Daily administration of LR-103 has not resulted in significant hypercalcemia to date. Dose escalation continues. No significant financial relationships to disclose.
Interferon-alpha (INF) and gefitinib or imatinib in patients (pts) with metastatic renal cell carcinoma (RCC)
Authors: Jac J. , Zhai Q. , Kareidy M. , Hernandez J. , Marsh L. , Amato R. J. 
Published: March 2020

14616 Background: Overexpression of EGFR is associated with aggressive clinical behavior in several solid tumors and is frequent in RCC. We recently found that the majority of RCCs express c-kit and PDGFR-beta. EGFR tyrosine kinase (TK) is inhibited by GEF, while IM is an inhibitor of Bcr-Abl, c-kit and PDGFR TKs. IFN has activity in MRCC and is used in front-line therapy. This trial evaluates time to progression (TTP) determined from time of study entry and response rate of INF in combination with GEF or IM, as well as tumor expression of c-kit and EGFR-beta. Methods: Pts with MRCC were assigned to a treatment arm: IFN/GEF or IFN/IM. Eligibility included: MRCC, any previous therapy, PS ≤2, adequate organ/marrow function and no active CNS involvement. Pts received IFN 3MU subcutaneously TIW on week 1, then 6MU TIW thereafter. GEF dose is 500 mg and IM 600 mg daily. Tumor response is assessed using RECIST every 12 weeks. Results: 16 MRCC pts (12 M/4 F) with a median age of 58 (24–77) have been enrolled. Histology: 6 papillary, 7 clear cell, 1 chromophobe, 1 collecting duct and 1 unclassified. 14 pts received IFN/GEF and 4 pts IFN/IM. Two pts crossed over from IFN/IM to IFN/GEF. Of 14 pts on IFN/GEF, 3 demonstrated a partial response (PR) and 7 had stable disease at 12 weeks. Of 6 papillary, 3 had PR. 8 pts progressed on IFN/GEF at a median of 20 weeks (1–36). 4 pts are still on treatment. On IFN/IM, 3 pts had stable disease at 12 weeks, 2 at 24. 2 pts progressed at 4 and 14 weeks, two crossed over to GEF at 24 weeks. Adverse events of IFN/GEF included skin rash and diarrhea and of IFN/IM skin rash, thrombocytopenia and leukopenia. Both arms had flu-like symptoms and fatigue. Conclusions: IFN/GEF and IFN/IM combinations are well tolerated. Preliminary results show the potential of delaying TTP in pts with MRCC. The observed high tumor response rate of the papillary type to IFN/GEF requires validation in a larger number of pts. Enrollment is ongoing. Updated response data and tissue correlates will be presented. [Table: see text]
Correlation of statin use and duration with increased survival in hormone refractory prostate cancer
Authors: Rich N. T. , Smith B. J. , Vaena D. A. 
Published: March 2020

14617 Background: Prior studies associated statin use with prevention and reduced progression of prostate cancer. (Platz et al, 96th AACR abst. 4374). However, the effects of statins in hormone refractory prostate cancer (HRPC) are unknown. We evaluated the impact of statins on survival of HRPC patients by comparing actual survival data with predicted survival using the Halabi nomogram (JCO 21:(7);1232). Methods: Using the Iowa City VA (ICVA) prescription database since 2001 along with chart review, we identified 28 consecutive patients who were prescribed statins when they had HRPC. Survival information, duration of statin use while HRPC, and Halabi nomogram variables were collected (Hb, PS, Alk Phos, Gleason, PSA). An LDH value of 90 U/L (low-normal at ICVA) was used for all patients, since LDH values were not available. Log-rank and and Cox regression analyses were performed. The outcome of interest was overall survival. Patients alive at last follow-up were censored. Statin use was treated as a time-dependent covariate in the regression analysis, and subject-specific predicted survival from the Halabi nomogram as another covariate. Results: 17 patients were alive and 11 had died. Median duration of follow-up for patients alive was 23 months. The observed vs. nomogram-predicted estimated median survivals were 36 vs. 17 months, respectively. Study patients significantly outlived their nomogram-predicted survival (p = 0.0004). Four patients had negative bone scans. 12 patients outlived their nomogram, 8 died before, and 8 were indeterminate (censored prior to their Halabi-predicted survival). Risk of death decreased with greater length of statin use (p = 0.02). When covariates for Halabi nomogram and statin use were both included in a multivariate regression model, neither was statistically significant, although similar point estimates for the relative risks were obtained. Conclusions: Statin use, and longer duration of use, significantly improved survival of HRPC patients in univariate analysis. The sample size limits the multivariate analysis. Evaluation of a time-dependent statin effect in HRPC could be considered in larger studies. No significant financial relationships to disclose.
The incidence of prostate cancer in patients under the age of 60 from an urban setting
Authors: Shum M. , Bodofsky E. , Skaff Z. , El-Khoury M. , Kankipati S. , Dalsania C. , Khemka V. , Parra R. , Dibiase S. , Somer R. 
Published: March 2020

14622 Background: Although the risk for developing prostate cancer increases with age, few studies have reported the incidence of prostate cancer in men younger than 60 from an urban setting. Methods: All patients diagnosed and treated for prostate cancer at The Cancer Institute of New Jersey at Cooper University Hospital in Camden County, New Jersey from January 1, 2004 to December 31, 2004 were retrospectively identified from our tumor registry. Age comparison at diagnosis was made utilizing the Cooper registry and the National Cancer Database (NCDB), 2001. Results: A total of 141 men (88 Caucasians, 37 African Americans, 14 Hispanic, and 6 unknown) with a median age of 64 years (range, 44–88 years) were diagnosed with prostate cancer in 2004. Staging revealed Stage II (118), Stage III (3), Stage IV (4), Stage unknown (16) cases. Median Gleason score was 6. 74 patients underwent radical prostatectomy, 50 had radiation, 30 received hormone therapy and 2 received chemotherapy. At diagnosis, 19.95% of the men were under 50 and 41.84% were under 60 years of age. Our dataset from these two age groups compared to NJ and US figures are noted below. Conclusions: When comparing the respective data sets from CINJ at Cooper to NJ and US utilizing the NCDB, there are striking differences with a higher incidence of prostate cancer in younger men. These incidences parallel those seen in other urban university teaching hospitals from the Healthcare Utilization Project (2005), where more patients under the age of 60 are being diagnosed with prostate cancer when compared to community centers. Subset analysis shows that our institution had a disproportionately larger number of African American men with prostate cancer which may relate to our culturally directed screening program, accounting for the higher incidence. These data support that hospital characteristics may impact age at diagnosis of prostate cancer, and further investigation is warranted. [Table: see text] No significant financial relationships to disclose.
The effect of androgen deprivation therapy (ADT) on cognition in men with prostate cancer
Authors: Allibhai Z. , Alibhai S. M. 
Published: March 2020

14626 Background: ADT plays a central role in the management of prostate cancer. However, there is emerging evidence that ADT use may adversely affect cognition. Given the long natural history of prostate cancer and the elderly population it predominantly affects, this may be an important survivorship issue in this population. Methods: We performed a MEDLINE search of English-language literature from 1966 to December 2005 and identified eight prospective studies that evaluated the effect of ADT on cognition and one study that investigated the effect of therapy on the cognition of patients receiving ADT. Due to differences in study design and outcomes, studies could not be combined meta-analytically. Results: Studies were small, ranging from 19–82 patients. ADT was used in the neoadjuvant setting in 2 studies, a neoadjuvant or adjuvant setting in 1 study, and in a palliative setting for high-risk disease in 5 studies. Controls were featured in 4 studies. Follow-up ranged from 6 to 13 months. A variety of cognitive domains were assessed (using traditional and computer-based neuropsychological tasks). Whereas 4 studies found worsening in one or more domains in patients over time, 4 studies showed either no worsening or improvement in one or more cognitive domains after ADT was instituted. No cognitive domain was consistently affected by ADT. Three of the studies included follow-up 3 months after ADT was stopped and all 3 showed at least some improvement in cognitive function. Short-term supplementation with estradiol did not improve cognitive function in 1 study. There were fundamental differences across studies in terms of patient populations, cognitive domains tested and specific tests used, and type of ADT. Other important limitations included small sample sizes, limited follow-up, and practice effects. Conclusions: The impact of ADT on cognitive function and its potential reversibility are unclear, and further studies are needed. In the meantime, clinicians and patients should continue to carefully weigh the potential benefits and risks of ADT when making treatment decisions. No significant financial relationships to disclose.