bluuebunny/crossref_metadata_2025_split huggingface dataset:
State laws and regulations covering fertility preservation for cancer patients
Authors: Vadaparampil S. T. , Lowrey K. M. , Miree C. A. , Eidson S. S. , Watson J. B. , Quinn G. P. 
Published: August 2020

9509 Background: Studies suggest up to 90% of cancer patients in their reproductive years may be at risk of permanent infertility. Yet, few utilize fertility preservation (FP) technologies. One barrier identified by patients and providers is the lack of insurance coverage for FP services. The goal of this study was to examine codified state policies related to infertility and assess their implications for cancer patients at risk for infertility due to treatment. Methods: A keyword search string was developed to identify statutes and administrative regulations of insurance coverage for FP in effect as of July 1, 2008, for the 50 states and the District of Columbia. Laws addressing a more general population but pertaining to cancer patients (e.g., policies addressing in vitro fertilization), were compiled using Lexis-Nexis. Data were analyzed by reviewing the “plain meaning” of the text, legislative/administrative history, and annotated case law. Legal reasoning and common rules of statutory construction and legislative interpretation were used. Findings were recorded using qualitative and dichotomous, quantitative indicators. Quality assurance reviews of all data were conducted and findings were compared with secondary sources. Results: As of July 1, 2008, 15 states (29.4%) had laws relating to insurance coverage for infertility or in vitro fertilization (IVF) procedures. Nine states (17.6%) mandated some type of insurance coverage for infertility treatments, 5 of which defined infertility. One state (CA) mandated an offer of coverage for infertility, but did not define it. For laws concerning IVF, 7 states (13.7%) mandated coverage; 1 state (TX) mandated an offer of coverage; and 2 states (CA and IL) specifically excluded IVF from a mandatory offer of coverage. No state laws or regulations addressed insurance coverage for FP methods specific to cancer patients. Conclusions: There is a strong argument for policies that require coverage for infertility of cancer survivors and FP options prior to treatment similar to mandatory coverage requirements for other side effects experienced by cancer patients (e.g., lymphedema, alopecia). No significant financial relationships to disclose.
Sexual function in male lymphoma survivors versus matched controls: Relationship to age, gonadal hormones, and quality of life
Authors: Kiserud C. E. , Schover L. R. , Fossaa A. , Dahl A. A. , Loge J. H. , Bjoero T. , Holte H. , Yuan Y. , Fossaa S. D. 
Published: August 2020

9510 Background: Sexual function in male lymphoma survivors (LS) was examined and compared to age-matched controls from the general population (CTR). Methods: The study includes 294 LSs, diagnosed 1980–2002, treated at the Norwegian Radium Hospital, ≤50 years at diagnosis, with recent gonadal hormone levels [testosterone (T), SHBG, LH, and FSH]. Sexual function was assessed using the Brief Male Sexual Function Inventory (BSFI) consisting of 11 self-report items covering five domains: sexual drive, erectile function, ejaculatory function, problem assessment and overall satisfaction. Lower scores indicate impaired sexual function. A total BSFI score (T-BSFI) was constructed by summing all items except overall satisfaction. Mean and median scores for the BSFI domains and T-BSFI were compared across age groups (21–39, 40–49, 50–59, 60–69 years at survey), gonadal hormone levels [normal (n=144), elevated FSH only (n=60), low T and/or elevated LH (n=90)], cancer treatment intensity, comorbidity, relationship status, fatigue score, mental distress (HADS) and quality of life (SF-36, mental and physical health components). Multivariate linear regression analysis was performed with T-BSFI as the dependent variable including independent variables significant in univariate analyses. Each LS was matched to two CTRs (n=506). Results: Valid T-BSFI scores were available for 253 LSs (86%). Median age at survey was 48 years, median duration of follow-up 15 years, and 78% were in a committed relationship. LSs aged 40–59 years had significantly lower T-BSFIs compared to their CTRs (p≤0.01). All BSFI domain scores and T-BSFI decreased significantly with ageing. LSs with low T and/or elevated LH had the lowest BSFI domain and T-BSFI scores. Survivors with normal hormone levels had the highest scores. Low T and/or elevated LH (p=0.03), age ≥50 years at survey (p≤ 0.001) and mental distress (p< 0.001) were significantly associated with male sexual dysfunction (T-BSFI) in the multivariate analysis. Conclusions: LSs aged 40–59 years reported poorer sexual function than age-matched CTRs. Impaired sexual function was significantly associated with age ≥ 50 years at survey, having low T and/or elevated LH and being distressed. No significant financial relationships to disclose.
Quantitative assessment of cardiorespiratory fitness, skeletal muscle function, and body composition in adults with primary malignant glioma
Authors: Jones L. , Friedman A. , West M. , Mabe S. , Fraser J. , Kraus W. , Friedman H. , Major N. , Reardon D. 
Published: August 2020

e13002 Background: The neuropsychological impact of malignant glioma is well documented; the physiological and functional effects are not known. We conducted a pilot study to quantitatively assess cardiorespiratiory fitness, skeletal muscle function, and body composition of patients with primary malignant glioma. Methods: Using a cross-sectional design, patients with clinically stable postsurgical (10 ± 7 days post surgery) high-grade glioma (HGG; n=25) and low-grade glioma (LGG) were studied. Participants performed a cardiopulmonary exercise test (CPET) with expired gas analysis to assess peak exercise capacity (VO2peak) and other parameters of cardiovascular function. Other physiological outcomes included skeletal muscle cross-sectional area (CSA; magnetic resonance imaging), isokinetic muscle strength (isokinetic dynamometer), and body composition (air displacement plethysmography). QOL was assessed by the Functional Assessment of Cancer Therapy-Brain scale (FACT-BR). Results: CPET was a feasible and safe procedure for malignant glioma patients with no serious adverse events. Peak VO2 indexed to total body weight and lean body mass for both groups was 13.0 mL.min-1 and 19 mL.min-1; the equivalent to 59% and 38% below age and sex-predicted normative values, respectively. Skeletal muscle isokinetic strength was significantly lower in HGG relative to LGG patients (83 vs. 125 Nm, p=.025) and predicted peak VO2 (r = 0.44, p<0.05). In patients with HGG, only self-reported exercise behavior was correlated with QOL (r = 0.42; p=.046) while sex (male) (r = 0.44; p=.037), lean mass (r = -0.41; p=.049), and VO2peak (r = -0.40; p=.052) were associated with fatigue. Conclusions: CPET is a safe and feasible tool to evaluate physical functioning in select patients with malignant glioma. Postsurgical glioma patients have markedly reduced exercise capacity, isokinetic strength and CSA. Muscle strength is an important contributor to poor VO2peak in this population. Prospective studies are now required to determine whether such abnormalities influence prognosis as well as test the effect of appropriately selected interventions to prevent and/or mitigate dysfunction. No significant financial relationships to disclose.
Assessment of diabetes mellitus (DM) as a risk factor for development of cisplatin-induced nephrotoxicity (CIN)
Authors: Weese J. , Sandhu P. D. , Mody A. , Ozer H. , Jafari M. , Tfayli A. H. , Kojouri K. 
Published: August 2020

e13537 Background: DM is the most common cause of kidney disease in the US, and it may increase the risk of CIN. In vivo studies however suggest that DM not only is not a risk factor for CIN, it may even be protective. This may be explained by dysfunction of organic cation transporter-2, the critical transporter for cisplatin uptake in proximal tubules, in diabetic kidneys. We conducted a case-control study to assess the relationship between DM and CIN. Methods: Records of all patients (pts) who received cisplatin between 1/1/00 and 12/31/06 at Oklahoma City VA Hospital were reviewed. DM was diagnosed if pt had (1) been taking anti-diabetic treatment, or (2) Hgb A1C ≥6.5%, or (3) ≥2 fasting outpatient serum glucose levels 126–199 mg/dl, or (4) ≥1 serum glucose level ≥200 mg/dl at any time, prior to receiving cisplatin. CIN was defined as increase in serum creatinine (SCr) by ≥50% above baseline and higher than upper limit of normal, after exclusion of other causes of elevated SCr, during or within 8 weeks of completion of treatment. Continuous variables are reported by means and ranges, and compared using 2-tailed student's t test. Odds ratio (OR) was calculated to compare risk of CIN between diabetics and non-diabetics. Results: Two hundred pts (2 females, 198 males) received cisplatin in the study period, 50 (25%) were diabetic. Distribution of age (years, diabetics: 62 [46–77]; non-diabetics: 60 [26–79], p = 0.18) and baseline SCr (mg/dl, diabetics: 1.0 [0.4–1.5]; non-diabetics: 1.0 [0.5–1.6], p = 0.86) were similar between the two groups. Overall 15% of pts (30 of 200) developed CIN. Risk of CIN was not different between diabetics (8 of 50 pts, 16%) and non-diabetics (22 of 150 pts, 14.7%); OR = 1.11 (95% CI = 0.46 to 2.67) (Table). Conclusions: DM was not shown to be a risk factor for development of CIN. This finding is consistent with in vivo data obtained through animal diabetic models. [Table: see text] No significant financial relationships to disclose.
An open-label, dose-escalating study of Maxy-G34, a novel potent, long-acting Pegylated G-CSF, compared with pegfilgrastim (PF) for the treatment of chemotherapy induced neutropenia (CIN)
Authors: Schwartzberg L. S. , Sankar S. L. , Apt D. , Goldstein E. , Vetticaden S. J. , Chitour K. , Gilfoyle D. , Kim S. , Keilholz U. , Possinger K. 
Published: August 2020

e14500 Background: rhG-CSF reduces the incidence and duration of CIN in patients (pts) receiving myelosuppressive chemotherapy. Maxy-G34 is a recombinant, modified human G-CSF, containing three 5 kD PEG groups. These modifications alter both renal and receptor mediated clearance, leading to a longer half-life and the potential for enhanced activity. Phase I studies demonstrated safety of Maxy-G34 in normal volunteers with a dose dependent rapidly reversible increase in the absolute neutrophil count (ANC). The effect of Maxy-G34 on CIN was evaluated in an open-label, active-comparator controlled, dose-ranging study. Methods: The primary efficacy endpoint was duration of severe, Grade 4 neutropenia (G4N) in treatment cycle 1. Adults with high-risk Stage I-IIIa breast cancer eligible for TAC chemotherapy received Maxy-G34 at 10, 30, 45, 60 or 100 μg/kg or the active control PF 6 mg, given sub- cutaneously 24-hours after each dose of TAC for 6 cycles. Blood samples were collected daily and analyzed at a central laboratory throughout each of the 21-day chemotherapy cycles to determine ANC and evaluate PK profile of Maxy-G34. Results: All dose groups of Maxy-G34 enrolled 6 pts each, except the 100 μg/kg group (3 pts), and the PF group (8 pts). The mean durations of G4N in cycle 1 were 2.2 days for 10 μg/kg, 1.8 days for 30 μg/kg, 0.8 days for 45 μg/kg, 2.2 days for 60 μg/kg, and 1.7 days for 100 μg/kg Maxy-G34 groups vs. 2.0 days for PF. The rate of FN was 2.6% across all Maxy-G34 doses vs. 4.2% for PF. CD34+ cell counts increased across Maxy-G34 groups following recovery from nadir with maximum concentration in treatment cycle 1 ranging from 25.8 to 133.3 cells/mL versus 49.6 cells/mL for PF. The average half-life and Cmax obtained after Maxy-G34 were approximately 2-fold higher than PF. Adverse events were consistent with those reported for G-CSF and TAC with no serious unexpected adverse events. Grade 3/4 AEs for Maxy-G34 was 9.5% vs. 8.5% for PF. No neutralizing antibodies related to Maxy-G34 were observed. Conclusion: Once-per-cycle Maxy-G34 appears to be effective in reducing CIN with no new safety signals. Further Phase II studies are planned. [Table: see text]
Pharmacogenetics of peripheral neuropathy in elderly patients (>65 years) with advanced gastric cancer receiving oxaliplatin-based chemotherapy within a randomized phase II study
Authors: Goekkurt E. , Al-Batran S. , Obermann L. , Pauligk C. , Homann N. , Hartmann J. T. , Moehler M. , Hofheinz R. D. , Gerhard E. , Stoehlmacher J. 
Published: August 2020

e14515 Background: Peripheral neuropathy (PNP) is a dose-limiting side effect of oxaliplatin based chemotherapy. High grade PNP may compromise quality of life especially in elderly patients (pts). A randomized multicenter phase II study was conducted to compare fluorouracil, leucovorin, oxaliplatin with or without docetaxel (FLO vs. FLOT, respectively) in elderly pts with advanced gastric cancer (AGC). Our purpose was to identify pharmacogenetic markers as predictors of high grade PNP within this study. Methods: 143 pts were enrolled in this study. Pts. were numerically >65 years or numerically >59 years but classified biologically >65 years as defined by an Instrumental Activities of Daily Living score of <8. PNP was classified according to an oxaliplatin specific scale. Genotyping was performed using PCR-based RFLP or TaqMan®-based allelic discrimination. 20 polymorphisms in 13 genes being part of the metabolism of the applied drugs or DNA repair were analyzed. Statistical analyses were based on stepwise multivariate cox regression models and included genotypes and clinical parameters. Results: Median age was 71 years (range 60–83). Pts received in median 6 cycles of treatment (range 1–12). 130 pts were evaluable for PN at time of analyses. Of these, 68 received FLO and 62 received FLOT. Cumulative grade 3 PNP occurred in 49% of pts without a significant difference between FLO and FLOT receiving pts (44% and 53%, respectively, p=0.4). Genotypes of TS and MTHFR could be identified as independent risk factors for grade 3 PNP by multivariate analyses. Pts carrying a TS promoter genotype known to be associated with low TS expression (2R/2R, 2R/3RC, 3RC/3RC) were at higher risk for developing grade 3 PNP compared to pts without one of these genotypes (OR 3.0 [95%CI 1.27; 7.06], p=0.01). Pts carrying MTHFR1298AC or CC genotypes were also at higher risk for experiencing grade 3 PNP compared to pts with the wildtype MTHFR-1298AA genotype (OR 3.1 [95%CI 1.26; 7.60], p=0.01). In fact, 89% of pts that experienced grade 3 PNP were carriers of at least one of these risk genotypes. Conclusions: Polymorphisms of TS and MTHFR might be associated with grade 3 PNP in AGC pts receiving oxaliplatin based chemotherapy. No significant financial relationships to disclose.
Phase I study combining an IGFR inhibitor (IMC-A12) and an mTOR inhibitor (temsirolimus) in patients with solid tumors or lymphoma
Authors: Naing A. , LoRusso P. , Mills G. , Berry D. , Doyle L. , Rohren E. , Burger A. , Chen H. , Busaidy N. L. , Kurzrock R. 
Published: August 2020

e14535 Background: IMC-A12 is a fully humanized IgG1/ lambda monoclonal antibody directed at the type I Insulin-Like Growth Factor Receptor (IGF-IR). Temsirolimus, an ester of the macrocyclic immunosuppressive agent sirolimus, is a cytostatic cell cycle inhibitor, which specifically inhibits the mammalian target of rapamycin (mTOR). A paradoxical increase in AKT activation by an mTOR inhibitor through an IGF-1R-dependent mechanism may compromise the therapeutic effect of mTOR inhibitors. Hence we evaluated the combination of temsirolimus and IMC-A12. Methods: This standard “3+3” design used a fixed dose of 25 mg IV weekly of temsirolimus with an escalating weekly dose of IV IMC-A12 at 3 mg/kg, 4 mg/kg and 6 mg/kg with no intrapatient dose escalation. The goal of this study is to define the MTD and to evaluate the biologic effects and metabolic activity of IMC-A12 and temsirolimus, individually and in combination. Patients with advanced solid tumors and lymphoma are eligible. No history of diabetes is allowed in dose escalation cohorts. Results: To date, 11 patients (4 males and 7 females, median age 47) with various solid tumor histologies have been enrolled across 3 dose cohorts with the current dose cohort at 6 mg/kg weekly IV of IMC-A12 and 25 mg weekly IV of temsirolimus. The MTD has not been determined. The most common grade 1 and grade 2 toxicities have been dysgeusia (n=5), fatigue (n=5), hyperglycemia (n=6), hypertriglyceridemia (n=6), leucopenia (n=4), mucositis (n=4), and ocular flashes of light (n=3). No grade 3 or 4 toxicity lasted more than 7 days (nausea n=1; vomiting n=1; thrombocytopenia n=1). Two patients (metastatic prostate cancer and metastatic breast cancer) demonstrated prolonged stable disease for 4 and 6 months, respectively. Conclusions: Preliminary data suggest that the combination is well tolerated and that it warrants further investigation. The expansion phase of this study will evaluate the biologic effects and metabolic activity of IMC-A12 and temsirolimus, individually and in combination, through the use of RPPA (Reverse Phase Protein Assays) and PET scans. [Table: see text]
Bioluminescence evaluation of efficacy of oncolytic treatment with Newcastle disease virus (NDV) in malignant pleural mesothelioma
Authors: Silberhumer G. , Brader P. , Wong J. , Zamarin D. , Serganova I. , Blasberg R. , Palese P. , Fong Y. 
Published: August 2020

e14536 Background: Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that arises from multipotent cells of the pleura. Chemotherapy and radiation have very limited therapeutic effects, and average survival time after diagnosis varies between 10 and 16 months. Immunotherapy, gene therapy (oncolytic viral therapy), and photodynamic therapy offer alternative treatment options, with promising results in animal studies. In the following study, the oncolytic efficacy of Newcastle disease virus (NDV(F3aa)-GFP) on MPM is tested and investigated by bioluminescence imaging. Methods: NDV(F3aa)-GFP was tested for viral cytotoxicity at different multiplicities of infection (MOI) against several mesothelioma cell lines in vitro by analyzing release of intracellular lactate dehydrogenase. For in vivo studies, MSTO 211H cells were transduced with firefly (Photinus pyralis) luciferase (FLuc)- encoding cDNAs (MSTO td 211H). Tumor-bearing animals (1e7 cells injected intrapleurally) were treated with either single or multiple doses of NDV(F3aa)-GFP (1e7 plaque-forming units) at different time points (days 1, 3, and 10) and followed by bioluminescence imaging. Results: Mesothelioma cell lines exhibited susceptibility to NDV lysis in the following order of sensitivity: MSTO 211H>MSTO td 211H>H-2452>VAMT>JMN. The cell lines H-2052, H-2373, and HMESO were not sensitive to viral treatment. In vivo studies with MSTO td 211H cells showed complete response to viral therapy in >75% of the animals, resulting in eradication of tumor detected by bioluminescence imaging at day 10 after treatment. Control animals were sacrificed after 23 days due to tumor burden, while >72% of the virally treated animals survived >50 days after tumor injection. No signs of toxicity were observed in the treatment group. In addition, multiple treatment showed a significantly better response compared with single treatment (p=0.005). Conclusions: NDV appears to be an efficient viral oncolytic agent in therapy of malignant pleural mesothelioma in a murine model, and warrants further investigation as a potential therapeutic agent. No significant financial relationships to disclose.
Extended phase I trial of the oral pan-Bcl-2 inhibitor AT-101 by multiple dosing schedules in patients with advanced cancers
Authors: Saleh M. N. , Pitot H. , Maleski J. , Leopold L. , Forero A. 
Published: August 2020

e14537 Background: Over-expression of Bcl-2 family proteins is common in human cancers. Initial trials of the oral, pan-Bcl-2 inhibitor AT-101 showed acute dose limiting toxicity of Gr 3–4 AST/ALT (MTD 40 mg/d) and ileus with prolonged dosing daily (QD) for 21/28 days per cycle (Saleh, NCI/EORTC, 2005; James, ASCO, 2006 and Saleh, ASCO, 2007). MTD in the QD schedule has been previously reported. In this study different dosing schedules of AT-101 were tested in adults with advanced cancers and final results for the pulse dosing schedule of twice a day for three days every other week (b.i.d. x 3d EOW) are being reported. Methods: Serial patient (pt) cohorts received AT-101 at escalating doses of 30–80 mg b.i.d. x 3d EOW. Adverse events (AEs) were graded by the NCI CTCAE v3.0. Efficacy was determined by RECIST. Results: 37 pts have been enrolled. Safety data is available on 34/37 pts. In this b.i.d. x 3d EOW dosing schedule, ileus/small bowel obstruction (SBO) occurred in 3 pts (one at each dose level of 30, 40 and 50 mg) and was the dose limiting toxicity for this schedule. Of note, the SBO that occurred at 30 mg was felt to be unrelated to study agent therefore, 30 mg b.i.d. x 3d EOW was the MTD determined for this schedule. The most common (>50%) grade 1–2 AEs included: nausea, vomiting, diarrhea, fatigue and anorexia. Grade 3–4 AEs occurring in > 2 pts include: nausea, abdominal pain, elevated AST (3 pts each), vomiting, fatigue, dehydration (4 pts each), hypokalemia (5 pts). Stable disease was reported in 13/37 (35%) pts. One pt with NSCLC continues on study with stable disease for 33 cycles and 2 additional pts were on study with stable disease for 18 and 9 cycles. The mean Plasma Cmax was 301 ng/ml (+ 477 ng/ml SD) and mean AUC for 30 mg b.i.d.x3d EOW was 1080 ng*hr/ml (+ 1990 ng/ml SD) with a median peak concentration at 4 hours post dose. Conclusions: Pulse dosing of AT-101 achieved an MTD of 30mg b.i.d. x 3d EOW and is associated with reduced toxicity than continuous daily dosing, and may be preferable in combination regimens. [Table: see text]