bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of educational materials about inherited breast cancer in black women
Authors: Pal T. , Gjyshi A. , Rivers D. , Rocchio E. , Garcia A. , Quinn G. P. , Vadaparampil S.
Published: August 2020

1536

Background: Current educational materials about inherited breast and ovarian cancer (HBOC) have not been culturally tailored for the Black community, which may contribute to lower levels of awareness about this topic. Through an academic and community partnership, realized through a Community Advisory Panel (CAP) comprised of breast cancer survivors, advocates, community leaders, and health care providers, this need was identified. Methods: Utilizing a phased approach implemented through this academic and community partnership, a culturally tailored brochure and booklet about HBOC for the Black community were developed and reviewed. To evaluate the brochure, three focus groups were conducted by race-concordant moderators. HBOC was discussed with Black women from diverse backgrounds, including those with and without breast cancer (n = 46). Summaries were created from audiotapes and handwritten notes and content was analyzed based on Grounded Theory, after which the brochure was revised. Similarly, revisions to the booklet were made based on feedback obtained about the brochure. Materials were then presented to the CAP for re-review. Results: From this iterative process, the key content identified as areas for improvement were: (1) Inclusion of breast cancer information specific to Black women; (2) Use of the term “Black”; (3) Inclusion of African American flag colors; (4) Clarification of the concept of genetic counseling; and (5) Enhancing relevance of information for young women. Conclusions: The CAP and study participants recognized the need for culturally relevant educational materials addressing HBOC in the Black community. Their feedback identified important areas for improvement which have been implemented in the design of a culturally tailored brochure that is available for widespread dissemination. Further evaluation of the booklet is currently in progress.

No significant financial relationships to disclose.
Trends in screening for prostate cancer
Authors: Eisinger F. , Morere J. , Pivot X. , Blay J. , Coscas Y. , Calazel Benque A. , Roussel C. , Viguier J.
Published: August 2020

1542

Background: Screening for prostate cancer is still in debate. In France, there is no financial barrier for individuals to be screened with the prostate-specific antigen (PSA) test, and there is no recommendation for mass screening. Methods: Two nationwide observational studies were carried out in France. The first one, EDIFICE 1, was conducted in 2005 among a representative sample of 1504 subjects aged between 40 and 75 years and a representative sample of 600 general practitioners (GPs). The second one, EDIFICE 2, was conducted in 2008 with the same methodology. Results: General population: In 2005, 36% of the interviewed male population aged between 50 and 75 years declared having undergone a screening test, compared to 49% in 2008 (OR = 1.63 CI95% 1.25; 2.12). Prostate cancer screening increased in all age groups, however, the most significant increase can be observed in the population aged between 50 and 54 years: 18% in 2005 versus 35% in 2008 (OR = 2.43 CI95% 1.31; 4.52). This trend for increasing testing will probably be confirmed in the future since 57% of males never screened plan to undergo a test, and only 16% of those who did screening plan to stop. The expected participation in the future will be close to 70%. Physicians: In 2005, 58% of GPs systematically recommended prostate cancer screening for their male consultants ages 50 to 74, in 2008 the figure is 65% (OR = 1.32 CI95%1.04; 1.66). For prostate cancer screening, a GP's gender has no significant impact. Systematic recommendation for both breast and colorectal cancer screening has an impact on recommending prostate cancer screening as well; OR = 2.9 (CI95% 2.0–4.4) and OR = 2.0 (CI95% 1.3–3.2) respectively. The GP's age is not associated with a higher rate of systematic recommendation. Conclusions: We have observed in France a significant growth in prostate cancer screening: more persons screened, more often, at a younger age. Despite the lack of consistent evidence, persons and GPs exposed to mass communication and campaign for breast and colorectal cancer screening might infer that screening is valuable for other conditions.

No significant financial relationships to disclose.
Epidermal growth factor receptor variant III (EGFRvIII) vaccine (CDX-110) in GBM
Authors: Heimberger A. B. , Archer G. E. , Mitchell D. A. , Bigner D. D. , Schmittling R. J. , Herndon J. E. , Davis T. , Friedman H. S. , Keler T. , Reardon D. A. , Sampson J. H.
Published: August 2020

2021

Background: Unlike conventional therapies for GBM, immunologic targeting of tumor-specific gene mutations allows precise eradication of neoplastic cells with reduced toxicity. EGFRvIII is a constitutively activated and immunogenic mutation not expressed in normal tissues, but widely expressed in GBM and other neoplasms. The cancer vaccine CDX-110 is comprised of an EGFRvIII-specific peptide sequence linked to keyhole limpet hemocyanin (KLH). Methods: A phase II multi-center trial assessed the immunogenicity and efficacy of CDX-110 in patients with newly-diagnosed, EGFRvIII+ GBM. After resection and radiation / TMZ, patients received CDX-110 vaccinations biweekly x 3, then monthly until tumor progression. Sequential cohorts received CDX-110 alone [ACTIVATE (n = 18)] or in combination with TMZ (200 mg/m2 x 5/28 days [ACT II A (n = 13)]) or (100 mg/m2 x 21/28 days [ACT II B (n=10)]). Results: Reversible systemic drug hypersensitivity reactions were seen in 1 ACTIVATE and 4 ACT II patients. Two patients had non-specific changes on MRI which were possibly due to the vaccine but which resolved. Despite grade 2 or 3 lymphopenia in all ACT II patients, EGFRvIII-specific immune responses were generated in all patients, and all immune responses were sustained or enhanced during subsequent TMZ cycles. Although ACT II B patients had more severe TMZ-induced lymphopenia, they developed greater EGFRvIII-specific immune responses (p = 0.028) when compared to ACT II A. EGFRvIII-specific IgG1 also increased in avidity with vaccination (Ka>>2x109M-1) in a randomly selected subset of 4 patients (p = 0.000068). Of the 23 recurrent tumors studied, 18 lost EGFRvIII expression (p = 0.001). There are no significant differences between ACT II A and B in estimated median TTP (18.5 vs. 14.9 months, p = 0.31) and OS (23.6 vs. 19.9 months, p = 0.75). ACTIVATE TTP (14.2 months) and OS (26.0 months) and ACT II TTP (15.2 months) and OS (23.6 months) compare favorably to a TMZ-treated, matched historical control group (TTP: 6.3 months; OS: 15.0 months). Conclusions: CDX-110 vaccination in patients with GBM appears very promising. TMZ enhances immune responses despite lymphodepletion. CDX-110 with simultaneous TMZ is under further investigation in a larger phase II trial.

[Table: see text]
Effect of granulocyte-macrophage colony stimulating factor (GM-CSF) administered with a multipeptide vaccine on circulating CD8+ and CD4+ T-cell responses: Outcome of a multicenter randomized trial
Authors: Slingluff C. L. , Petroni G. R. , Olson W. C. , Smolkin M. E. , Ross M. I. , Haas N. B. , Grosh W. W. , Boisvert M. E. , Kirkwood J. M. , Chianese-Bullock K. A.
Published: August 2020

3008

Background: GM-CSF administered locally with vaccines can augment T-cell responses in animal models. Human experience with GM-CSF has mostly occurred in uncontrolled or nonrandomized trials. Thus, a multicenter prospective randomized phase II trial was performed to determine whether local administration of GM-CSF augments immunogenicity of a multipeptide vaccine administered in an emulsion with an incomplete Freund's adjuvant (IFA). A second component of the trial was designed to assess whether the vaccine administered in two sites is more immunogenic than in a single site. Methods: 121 eligible and evaluable patients with resected stage IIB-IV melanoma were administered a sequence of multipeptide vaccines, each consisting of 12 MHC Class I-restricted melanoma peptides (12MP) to stimulate CD8+ T cells, plus an HLA-DR restricted tetanus helper peptide to stimulate CD4+ T cells. Peptides were emulsified with IFA, with or without GM-CSF. T cell responses were assessed by IFN-gamma ELIspot assay and tetramer analysis, weekly x 8. Clinical outcome was evaluated for all patients. Results: Vaccination was well-tolerated, and each peptide was immunogenic. Overall CD8+ T-cell response rates to the 12MP (days 1–50), for patients vaccinated with or without GM-CSF were 43% and 75%, respectively (p < 0.001), and response magnitude was almost twice as high in patients without GM-CSF. Class I MHC tetramer analyses corroborated the functional data. There was also a greater CD4+ T-cell response to the tetanus helper peptide without GM-CSF than with it (95% and 77%, respectively, p = 0.005). There was no significant difference in immune response rates by the number of vaccine sites. For the entire patient group, 3-year overall and disease-free survival estimates [95% CI] were 76% [67, 83%] and 52% [43, 61%], respectively. There have been too few events to assess differences in clinical outcome by study arm. Conclusions: High immune response rates were achieved with this multipeptide vaccine, but CD8+ and CD4+ T-cell responses appear to be partially suppressed with addition of GM-CSF. These data challenge the value of local GM-CSF as a vaccine adjuvant in humans.

[Table: see text]
Association of plasminogen-activator inhibitor 1 (PAI-1) 4G/5G gene polymorphism with survival and chemotherapy-related vascular toxicity in non-seminomatous testicular cancer (TC)
Authors: de Haas E. C. , Zwart N. , Meijer C. , Boezen H. M. , Suurmeijer A. J. , van der Meer J. , Hoekstra H. J. , van Leeuwen F. E. , Sleijffer D. T. , Gietema J. A.
Published: August 2020

5083

Background: High PAI-1 expression by tumor has been associated with poor prognosis in different cancer types, while high systemic PAI-1 levels may increase the risk of vascular thrombosis. We investigated whether the 4G/5G del/ins polymorphism in the PAI-1 promoter (rs1799889; 4G might lead to higher transcription), is associated with differences in survival and prevalence of cardiovascular events in TC. Methods: Data were collected on survival and cardiovascular events (venous thromboembolism [VTE] and coronary heart disease [CHD]) of TC patients treated with standard platinum based chemotherapy from 1977–2004. PAI-1 genotype was determined from non-tumor genomic DNA by a Taqman SNP assay. Genotypes were compared for survival (Kaplan-Meier curves + log-rank and Cox-regression analysis), disease outcome (logistic regression) and prevalence of VTE and CHD (χ2-test). Results: Data are available for 324 patients with median follow-up of 10 yrs (range 0–28). The 3 genotypes 4G/4G (n = 84), 4G/5G (n = 164), and 5G/5G (n = 76) do not differ in age and initial chemotherapy regime. However, the 4G/4G variant shows a higher prevalence of International Germ Cell Cancer Classification (IGCCC) poor prognosis compared to 4G/5G + 5G/5G (24% vs 10%; p = 0.003), as well as a decreased TC related survival compared to 4G/5G + 5G/5G (83% vs 94%; p = 0.001) with a hazard ratio of 2.68 for TC related death (95%CI 1.26–5.72; adjusted for IGCCC p = 0.011). In addition, the 4G/4G variant shows an odds ratio of 3.35 for refractory TC and early relapses (<2 yrs) (95% CI 1.48–7.58; p = 0.004). The 3 genotypes do not differ significantly in prevalence of VTE (4G/4G 11.9%, 4G/5G 8.5%, 5G/5G 7.9%; p = 0.616) and CHD during/after chemotherapy (4G/4G 6.0%; 4G/5G 4.9%; 5G/5G 2.6%; p = 0.594). Conclusions: The 4G/4G variant of the PAI-1 4G/5G gene polymorphism is associated with IGCCC poor prognosis, reduced survival and higher prevalence of refractory disease and early relapses. No effect on vascular toxicity was found. The 4G/4G variant of the PAI-1 gene may be an unfavorable prognostic factor as well as an unfavorable predictive factor for response to chemotherapy in patients with TC.

No significant financial relationships to disclose.
Short-term (ST) versus long-term (LT) hormone treatment (HT) in combination with radiotherapy (RT) for locally advanced prostate cancer (LAPC): Meta-analysis of randomized trials (RCTs)
Authors: Cuppone F. , Bria E. , Giannarelli D. , Milella M. , Ruggeri E. M. , Sperduti I. , Nisticò C. , Terzoli E. , Cognetti F. , Carlini P.
Published: August 2020

5128

Background: Hormone suppression plus RT is able to significantly decrease the recurrences and the mortality of patients (pts) affected by LAPC. In order to determine if difference exists between ST-HT (HT ≤6 months), and LT-HT (HT ≥8 months) in combination with RT for LAPC, a literature-based meta-analysis was conducted. Methods: Event-based relative risks (RR) with 95% confidence intervals (CI) were derived through a random-effect model. Differences in primary (biochemical failure, BF, and cancer-specific survival, CSS), and secondary outcomes (overall survival, OS, and pattern of recurrence, local or distant, LR/DM) were explored. Absolute differences (AD) and the number of patients needed to treat (NNT) were calculated. Heterogeneity test, a meta-regression analysis with clinico-pathological predictors for outcomes and a correlation analysis for surrogate end-points were conducted as well. Results: Four trials (3,148 patients) were gathered. Data were available for all RCTs only for BF; patient population ranged from 297 to 1,521 pts. Three predictors were identified: median PSA (range 9.5–20.35), Gleason score 7–10 (27–55% pts/trial) and T3–4 (13–77% pts/trial). None of the selected predictors did significantly affect any outcomes. A significant correlation and trend between the log of the BF-RR and DM and OS were found (p=0.029 and p=0.07, respectively). Conclusions: Although with significant heterogeneity (reflecting different patient’ risk stratifications), LT-HT seems to significantly decrease biochemical, local and distant recurrences, and increase cancer specific survival in comparison with ST-HT. Balancing these advantages with toxicities and costs represents the next step of the current analysis.

[Table: see text]

No significant financial relationships to disclose.
Postrandomization analysis assessing survival following radiation therapy (RT) with or without 6 months of androgen suppression therapy (AST) for localized prostate cancer (PCa)
Authors: Nguyen P. L. , Chen M. H. , Beard C. J. , Loffredo M. , Renshaw A. A. , Suh W. W. , Kantoff P. W. , D'Amico A. V.
Published: August 2020

5129

Background: 6 months of AST+RT was shown to improve survival vs. RT alone in men with unfavorable-risk localized PCa, but it is unknown if this benefit applied to all risk subgroups. Methods: Among 206 men with clinical T1b-T2b PCa and at least 1 unfavorable feature (PSA>10 or Gleason >=7 or MRI evidence of T3 disease) randomized to 70Gy of RT with or without 6 months of AST, we performed post-randomization subgroup analyses within four subgroups defined by both risk group (high risk [Gleason 8–10 or PSA >20] or intermediate risk [all others]), and by ACE-27 comorbidity level (no/limited comorbidity or moderate/severe comorbidity). Within the 4 subgroups a log-rank test was used to compare Kaplan Meier estimates of survival (requiring p < 0.05/4 or p < 0.0125 to adjust for multiple comparisons) and within the 2 risk groups we used Cox multivariable analysis (MVA) to assess the association of treatment with the risk of death after adjusting for known prognostic factors. Results: After a median follow-up 8.2 yrs, 74 men died. In men with no or minimal comorbidity, estimates of survival were significantly higher among those who received AST+RT vs. RT alone, regardless of whether they had intermediate risk disease (90.9 vs. 85.8% at 7yrs, p = 0.009) or high-risk disease (88.9% vs. 51.2% at 7yrs, p = 0.007). In men with moderate or severe comorbidity, no difference in survival was observed after AST+RT vs. RT in intermediate risk (p = 0.2) or high risk (p = 0.5). After adjusting for known prognostic factors, treatment with RT as compared to AST+RT was associated with an increased risk of death in men with intermediate (AHR: 3.0 [95% CI: 1.3 to 7.2]; p = 0.01) and high risk disease (AHR: 3.3 [95% CI: 0.94 to 11.3]; p = 0.06) in a model that adjusted for the interaction between treatment and comorbidity. Conclusions: Among men with T1b-T2b prostate cancer who have no or minimal comorbidity, the addition of 6 months of AST to RT was associated with improved survival in men with both intermediate risk and high-risk disease. Among men with moderate to severe comorbidity, neither risk group appeared to benefit from the addition of AST.

No significant financial relationships to disclose.
Use of pain at baseline and pain progression to predict overall survival (OS) in patients (pts) with docetaxel pretreated metastatic castration-refractory prostate cancer (CRPC): Results from the SPARC trial
Authors: Sartor A. O. , Petrylak D. , Sternberg C. , Witjes F. , Halabi S. , Berry W. , Petrone M. , McKearn T. , Noursalehi M. , George M.
Published: August 2020

5148

Background: First-line chemotherapy trials have reported that pain predicts OS in CRPC. We report relationships between OS and baseline pain –a major component of CRPC patient reported outcomes (PRO) –and pain at progression, for docetaxel pre-treated patients in a second-line chemotherapy trial in CRPC. Methods: Docetaxel pre-treated pts (N = 488) were analyzed from the multi-national, randomized, double-blind SPARC trial, comparing second-line satraplatin + prednisone vs placebo + prednisone in 950 metastatic CRPC pts. Daily pain intensity and narcotic analgesic use were recorded as a PRO from one week prior to randomization until end-of-study. Pain was measured by the 6-point Present Pain Intensity (PPI) component of the McGill-Melzack Pain Questionnaire. After randomization, weekly PPI scores were calculated as the mean of the daily PPI scores (using ≥3 daily measurements/week). Baseline pain was the mean of ≥5 daily PPI scores recorded during 7 days preceding randomization. An independent blinded review committee (IRC) determined pain progression (defined as an increase in weekly PPI score ≥1 point from baseline or ≥2 points from nadir, or a >25% increase from baseline in weekly average analgesic score for ≥2 consecutive weeks). To examine the effects of pain on OS, pts were categorized as “no pain” (PPI ≤1) or pain (PPI ≥2) by baseline assessment; and, as either pain progressors or pain non-progressors. Results: Shortened OS was observed in pts with baseline pain; median survival of 178 pts with pain was 44 weeks vs 72 weeks for 287 pts without pain (Strat. Log-rank p < 0.0001, Strat. HR 0.59; 95% CI: 0.48–0.74). IRC found disease progression in 414 (84.4%) of the docetaxel pre-treated pts with 196 of these pts showing pain progression. Pain progression was strongly linked to OS with 196 pain progressors having median OS of 47 weeks compared to 71 weeks for 292 pain non-progressors (Strat. Log-Rank p = 0.0022; Strat. HR 0.71; 95% CI: 0.57–0.87). Conclusions: Both pain at baseline and pain at progression are important prognostic indicators of OS in metastatic CRPC pts failing first-line docetaxel.

[Table: see text]
Correlation of PIK3CA mutation-associated gene expression signature (PIK3CA-GS) with deactivation of the PI3K pathway and with prognosis within the luminal-B ER+ breast cancers
Authors: Loi S. , Haibe-Kains B. , Lallemand F. , Pusztai L. , Bardelli A. , Gillett C. , Ellis P. , Piccart-Gebhart M. J. , Phillips W. A. , McArthur G. A. , Sotiriou C.
Published: August 2020

533

Background: The phosphathidylinositol-3-kinase (PI3K) signaling pathway is frequently deregulated in tumor biology and is an attractive target for cancer therapy. Our aim was to characterize the molecular and clinical outcome effects of PIK3CA mutations in breast cancer (BC). Methods: We analyzed 173 BC samples for PIK3CA mutations. Corresponding gene expression profiles were used to understand its effects on the PI3K pathway. We validated a PIK3CA-GS in 2 independent BC cohorts (n = 183) with known PIK3CA mutation status and evaluated its correlation with clinical outcome in 1748 BC samples stratified by treatment and subtype. Results: 26% of BCs had a PIK3CA mutation. Tumors with PIK3CA mutation demonstrated a distinct gene expression signature (p = 0.03 after 1000 perm). In 2 datasets it could discriminate PIK3CA mutation carriers from wild-type (ROC 0.68, 0.71, p = 0.001for both). However, the PIK3CA-GS was correlated with deactivation of the PI3K pathway probably through a negative feedback loop. This observation was supported by: 1) the PIK3CA-GS was significantly correlated with gene expression changes induced by PI3K inhibitors (Connectivity Map, Gene set enrichment analyses) and 2) the PIK3CA-GS was anti-correlated with a GS of PTEN loss (R = -0.3; Saal et al, 2007). Higher levels of the PIK3CA signature were observed in HER-2+ and estrogen receptor positive (ER+), luminal BC subtypes. Whilst there was no association with mutation status alone and prognosis, increasing expression of the PIK3CA-GS (suggesting deactivation) was significantly associated with better clinical outcome in both untreated (p = 0.04) and particularly ER+, luminal-B, tamoxifen only-treated (p = 0.004) BC. Multivariate analysis (HR: 0.4; 95%CI: 0.3–0.7; p = 0.002) confirmed that the PI3KCA-GS provided independent prognostic information. Conclusions: Paradoxically, the PIK3CA-GS correlates with inhibition of the PI3K pathway in ER+ BC and identifies a subgroup of luminal B BCs with a favorable outcome. The PIK3CA-GS may be a better indicator of PI3K pathway dysfunction than mutation status, potentially indicating patients who may benefit from combined endocrine therapy and PI3K inhibition.

No significant financial relationships to disclose.
Underuse of breast cancer adjuvant treatment: Patients' knowledge, beliefs, and medical mistrust
Authors: Bickell N. , Weidmann J. , Fei K. , Leventhal H.
Published: August 2020

6521

Background: We surveyed breast cancer patients in New York City to understand why women did not receive radiotherapy (RT) following lumpectomy, chemotherapy, or hormonal therapy for hormone receptor negative or positive tumors >1 cm, respectively. Methods: 258 New York City women recently surgically treated for a new primary stage I or II breast cancer were surveyed about their experience of care, knowledge and beliefs about breast cancer and its treatment. Adjuvant treatment data were obtained from in and out-patient chart abstraction. Principal components factor analysis was used to create scales of adjuvant treatment beliefs and knowledge, medical mistrust, physician communication about treatment and social support. Scales were scored to 100. Bivariate and multivariate analyses were conducted to determine differences between treated and untreated women; odds ratios were converted to adjusted relative risks. Results: Compared to treated women, untreated women were less likely to know adjuvant therapies increase survival (66 vs 75; p < 0.0001), had greater mistrust (64 vs 53; p = 0.001), and less self efficacy (92 vs 97; p < 0.05); there was no association between physician communication of treatment information and patient knowledge and beliefs about adjuvant treatment (r = 0.8; p = 0.21). Multivariate analysis found that compared to those who were treated, untreated women were more likely to be 70 years or older (OR = 4.46; 95%CI: 1.9–10.7), more likely to have a comorbidity (OR = 3.39;1.5–7.9), more likely to express mistrust in the medical delivery system (OR = 1.03;1.0–1.1), and less likely to believe adjuvant treatments beneficial (OR = 0.91; 0.87–0.96) (model c = 0.84; p =< 0.0001). Conclusions: Patient knowledge and beliefs about treatment and medical mistrust are mutable factors associated with underuse of adjuvant therapies. Despite physicians' discussion of treatment, patients do not have a clear understanding of treatments' benefits and risks. This disconnect between what is said and what is heard may be mediated and addressed by dealing with patients' trust in and concerns about the medical delivery system.

No significant financial relationships to disclose.
Adjuvant trastuzumab for breast cancer outside of clinical trials: Cardiotoxicity and economic evaluation
Authors: Snow S. , Skedgel C. , Rayson D. , Thompson K. , Sellon M. , Barnes P. , Jeyakumar A. , Younis T.
Published: August 2020

6585

Background: Clinical and economic evaluations of adjuvant trastuzumab (aTZ) in breast cancer (BC) are based on clinical trial outcomes. Population based studies however provide unique opportunities to examine outcomes in a real world setting. We previously examined aTZ uptake in all patients diagnosed with stage I-III BC over one year in Nova Scotia, Canada (Snow et al SABCS 2007). We now report cardiotoxic events (CE) and an economic evaluation based on our previous cohort. Methods: A retrospective chart review of all patients treated with aTZ was conducted to abstract clinical-pathological characteristics, treatment details, CEs/significant LVEF declines, and associated medical resource utilization (MRU). Cardiac risk scores (CRS) (Rastogi et al ASCO 2007) were also computed for all patients. Biserial correlation was performed to detect differences in CRS scores among subgroups. Costs associated with aTZ were based on MRU; unit costs were derived from the literature and local resources. A probabilistic model (Skedgel et al ASCO 2008) was utilized to examine the cost per quality adjusted life year gained (QALYG) at a 25-year horizon with budget impact calculated in 2009 Cdn $. Results: Of a total population of 630 patients with stage I-III BC, 37 (5.9%) received aTZ as per HERA trial treatment schedule; two (5.4%) had a CE (one death) and five (13.5%) experienced significant LVEF decline. CEs and LVEF declines were higher in patients with baseline LVEF 50–55% vs. > 55% (10% vs. 4% and 20% vs. 11%, respectively). CRS accurately predicted the observed CE rate, and was also predictive of significant LVEF decline (p = 0.056). Compared to previous estimates, the mean cost per patient of $46,070 (95%CI: $38,541-$54,422) was lower and the cost-utility of $60,439/QALYG was more favourable. Based on the observed aTZ utilization rate, a budget impact of $59.9m (95%CI: 42.5 m-79.9 m) for 2009 in Canada is expected. Conclusions: CEs and significant LVEF declines in this population based cohort appear comparable to that reported in clinical trials. Based on the aTZ costs per patient in this study, the cost-utility of aTZ is more favourable than previous estimates although the associated budget impact remains substantial.

No significant financial relationships to disclose.
Growth hormone deficiency and cardiovascular risk factors in childhood cancer survivors
Authors: Gujral K. , Petryk A. , Steffen L. , Baker K. , Perkins J. , Kelly A. S. , Zhou X. , Sinaiko A. , Moran A. , Steinberger J.
Published: August 2020

6614

Background: Childhood cancer survivors (CCS) have a high frequency of growth hormone deficiency (GHD) and risk of early cardiovascular disease (CVD). This study examined the relations between GHD and risk factors for CVD in CCS. Methods: Anthropometrics, blood pressure, lipids, growth hormone (GH) stimulation test, dual-energy x-ray absorptiometry, abdominal CT, and insulin resistance (IR) (euglycemic, hyperinsulinemic clamp - low M/lbm signifies IR) were obtained in 174 CCS, mean age 15±2 years and 89 healthy sibling controls, mean age 13.5±3 years. Linear regression evaluated the relations between GHD and CVD risk factors, adjusted for sex, age, pubertal stage, and body mass index (BMI) or visceral fat. Results: 62 CCS (36%) had GHD. There were no significant measurement differences between non-GHD CCS and controls. Compared to controls, GHD CCS who never received GH (N = 34) had greater BMI (24.8 vs 20.8 kg/m2, p < 0.0001), percent body fat (36.1% vs 25.8%, p < 0.0001), visceral fat (34.8 vs 19.6 cm2, p < 0.0001), and triglycerides (TG) (120.2 vs 83.8 mg/dL, p = 0.001) and were more IR (M/lbm 11.1 vs 14.2 mg/kg/min, p = 0.0006). Adjustment for BMI and visceral fat did not change the IR or TG results. GHD CCS currently on GH had lower BMI (21.9 kg/m2, p = 0.02), percent body fat (31.2%, p = 0.08), and visceral fat (26.5 cm2, p = 0.03) compared to those not treated. IR and TG were not different between treated and not treated GHD CCS. Conclusions: GHD is a common finding in CCS and is significantly associated with adiposity, IR, and elevated TG.There is a suggestion that GH treatment had a positive impact on adiposity, but not IR and TG levels. These study findings imply that CVD risk factors are present in CCS with GHD independent of body fatness, suggesting that the cancer diagnosis or treatments received may lead to early cardiovascular disease in childhood cancer survivors.

No significant financial relationships to disclose.
A comparison of patient-reported outcomes (PROs) in National Cancer Institute-sponsored cancer treatment trials conducted during two time periods: 1999–2003 and 2003–2008
Authors: O'Mara A. M. , Denicoff A. M. , Reeve B. , Burns R. , Trimble T.
Published: August 2020

6618

Background: Over the past decade, the U.S. National Cancer Institute (NCI) support for incorporating Patient-Reported Outcomes (PROs) into disease treatment clinical trials has grown considerably, both in the number of trials, as well as the types of research questions being addressed and the measures used to answer the questions. This presentation will compare the breadth of NCI supported Phase III treatment trials in breast, colo-rectal, lung, and prostate cancers that include PRO secondary endpoints activated during two time periods: 1999–2003 and 2003–2008. Both time periods will be compared to identify the number and type of PRO measures; in addition the targeted PRO domain will be examined by cancer site. Methods: For this study, PRO was broadly defined to include any self-report questionnaire that gathered data on the potential impact that disease treatment might have on patient functioning, quality of life, or symptoms. Using the terms, 'protocol title, lead disease, phase III, quality of life, and instrument name,’ a search was conducted of the NCI database containing breast, colo-rectal, lung, and prostate Phase III treatment trials activated during the two time periods. If a scale was used more than once or if different versions of the scale were used, i.e., FACT-G and FACT-BR, it was only counted once. Results: Between 1999 and 2003, 42 phase III trials in the four major cancers were activated, with 15 trials having one or more PROs as secondary endpoints. Between 2003 and 2008, 50 phase III trials in the four major cancers were activated, with 28 trials having one or more PROs as secondary endpoints. Although the data reveal a 20% increase in the number of phase III trials in the 4 diseases between the two time periods, the number of trials with PRO endpoints has doubled. Conclusions: This significant increase in the use of PROs in phase III trials gives investigators additional data to fully analyze the impact of new treatments. These PRO data will provide researchers, clinicians, and future patients with a more in-depth understanding of the potential for new cancer therapies and technologies to extend both the quantity and quality of life.

No significant financial relationships to disclose.
Subcutaneous omacetaxine mepesuccinate in imatinib-resistant chronic myeloid leukemia (CML) patients (Pts) with the T315I mutation: Data from an ongoing phase II/III trial
Authors: Cortes J. E. , Khoury H. J. , Corm S. , Nicolini F. , Schenk T. , Jones D. , Hochhaus A. , Craig A. R. , Humphriss E. , Kantarjian H.
Published: August 2020

7008

Background: Omacetaxine (OM), a first-in-class cetaxine shows clinical activity against Ph+ CML with a mechanism independent of tyrosine kinase inhibition. Currently available tyrosine kinase inhibitors (TKIs) have no activity against T315I. Methods: Adult Pts with T315I+ CML following TKI failure received OM induction at 1.25 mg/m2 subcutaneous (SC) twice daily (BID) for 14 days every 28 days followed by maintenance at 1.25 mg/m2 SC BID for 7 days every 28 days (maintenance after at least one induction cycle and achievement of hematologic response). Results: 66 pts (39 chronic [CP], 16 accelerated [AP] and 11 blast phase [BP]) have been enrolled. All had failed prior imatinib and 80% failed ≥2 prior TKIs. Median age is 58 yrs. Median disease duration is 58 mos. OM is well tolerated with transient myelosuppression as the primary toxicity. Grade 3/4 non-hematologic events are diarrhea (2%) and fatigue (4%). Efficacy data are available for 44 Pts. In CP Pts, the median number of cycles is 4 (1–22) with 39% having received ≥ 6 cycles of therapy; 64% of Pts have had the T315I clone reduced to below detection limits; the 2-year progression free survival is 70%. Conclusions: Omacetaxine in T315I+ CML Pts results in de-selection of the T315I clone and induces hematologic and cytogenetic responses.

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Prognostic significance of leukopenia at the time of diagnosis in acute myeloid leukemia (AML)
Authors: Arellano M. L. , Winton E. , Pan L. , Souza L. , Sunay S. , Lima L. , McLemore M. , Heffner L. T. , Langston A. , Khoury H. J.
Published: August 2020

7070

Background: In contrast to the poor prognosis associated with hyperleukocytosis, the prognostic significance of leukopenia at the time of diagnosis of AML is unknown. Methods: Single institution retrospective analysis of 225 consecutive, newly diagnosed AML patients (pts), homogeneously treated between July 1996 and February 2005; and divided into 2 groups based on presenting WBC: < 2,000/uL (30) and > 2,000/uL (195). Simultaneously obtained peripheral blood and marrow blasts were analyzed for cell surface expression of CD34, cKit, CXCR4, PCAM, VLA-2, VLA-3, VLA-4, VLA-5, and FLT3 using flow cytometry. Results: Patients’ characteristics (gender, secondary vs. de novo, and cytogenetic [CTG] risk) were comparable between the 2 groups. Leukopenic AML pts were older (median 56 vs. 53 years, p = 0.02), and had lower induction complete remission [CR] rates: 63% vs. 81% (p = 0.03) by univariate analysis. Induction mortality was 0% for leukopenic and 5% for non-leukopenic pts. In primary refractory pts, median survival was longer for leukopenic (11) vs. non-leukopenic (34) pts: 137 vs. 81 d (p = 0.026). Median follow-up was 22 mos. Event-free (EFS), disease-free (DFS), and overall survivals (OS) were lower in the leukopenic group: 12 vs. 14; 14 vs. 17; and 17 vs. 19 mos, respectively; but did not reach statistical significance. By multivariate analysis, age (p < 0.0001) and CTG risk group (p < 0.0001) were independent predictors of OS, while CTG risk group predicted RFS (p < 0.0001). The level of expression of cell surface adhesion molecules on blood and marrow blasts was comparable for the 2 groups. Conclusions: AML pts presenting with leukopenia have comparable outcomes to those presenting with normal or high WBC despite a lower likelihood of achieving remission. Leukopenic AML did not have over-expression of cell surface adhesion molecules.

No significant financial relationships to disclose.
Insulin-like growth factor receptor 1 (IGF1R) protein expression, mRNA expression and gene copy number in operable non-small cell lung cancer (NSCLC)
Authors: Dziadziuszko R. , Merrick D. T. , Witta S. E. , Mendoza A. D. , Szostakiewicz B. , Rzyman W. , Jassem J. , Bunn P. A. , Varella-Garcia M. , Hirsch F. R.
Published: August 2020

7524

Background: IGF1R is a promising target for NSCLC therapy. We have evaluated IGF1R protein expression, mRNA expression and gene copy number in primary tumors from surgically treated NSCLC patients (pts) as a reference for correlative biomarker studies in trials using IGF1R inhibitors. Methods: The study included 189 consecutive NSCLC pts who underwent curative pulmonary resection. There were 24% females, 54% squamous cell carcinomas (SCC), 29% adenocarcinomas (AC), 3% large cell carcinomas, 14% other histologies; p stage I: 41%, pII: 22%, pIII: 32% and pIV: 4%. IGF1R expression was evaluated in tissue microarrays by immunohistochemistry (IHC) with Ventana CONFIRM (N=179) and Novus (#NB600–559) anti-IGF1R Ab scored by two observers (H score 0–400). IGF1R gene copy number was assessed by FISH using customized probes (N=181). IGF1R gene expression was evaluated using qRT-PCR from 114 corresponding fresh-frozen samples. Results: Patterns of IHC staining were different for the Ventana and the Novus Ab (inverse correlation, r=-0.16, p=0.04, N=177). IGF1R protein expression detected by Ventana Ab (> median score) was more frequent in SCC (76%) than AC and other histologies (14%, p<0.001) and in pts with higher stage (p=0.03) but was not associated with survival (p=0.46). IGF1R H score by Ventana Ab, but not by Novus Ab, correlated with mRNA expression (r=0.37, p<0.001). IGF1R mRNA expression tended to be higher in SCC than in other histologies (p=0.089), but did not associate with other clinical features or survival (p=0.73). According to criteria previously established for EGFR, IGF1R gene copy number by FISH showed 5 tumors with gene amplification (2.8%), 43 tumors - high polysomy (23.8%), 87 tumors - low polysomy (48.1%), and 46 tumors - trisomy/disomy (25.4%). Pts with gene amplification/high polysomy had 3-yr survival of 60% (95% CI 47% - 74%) vs. 48% (38% - 59%) for low polysomy and 35% (21% - 49%) for trisomy/disomy pts (p=0.016). Prognostic value of IGF1R gene copy number was confirmed in the multivariate analysis. Conclusions: IGF1R protein expression is higher in SCC. IGF1R protein and gene expression does not associate with survival, whereas high IGF1R gene copy number associates with better prognosis in operable NSCLC.

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Effects of immediate compared with delayed gefitinib after front-line chemotherapy in Chinese with advanced non-small cell lung cancer
Authors: Wang J. Z. , An T. T. , Yang L. , Bai H. , Zhao J. , Duan J. C. , Li P. P. , Wu M. N. , Sun H. , Yang P. , Wang J. Z.
Published: August 2020

8069

Background: To compare therapeutic effects of immediate vs. delayed gefitinib used for advanced non-small cell lung cancer (NSCLC) patients who obtained disease control (DC) after front-line chemotherapy in Chinese population. Methods: The study included 121 Chinese with advanced NSCLC treated with standard chemotherapy and obtained DC followed by either immediate gefitinib (66 cases) or delayed gefitinib, i.e. when tumors progressed (55 cases). The disease control rate (DCR), median progression-free survival time (PFS), median overall survival time (OS) of the two groups were analyzed. The impact of EGFR mutation status on the treatments was also evaluated. Results: The median PFS of patients treated in the immediate treatment setting was significantly longer than that of patients without gefitinib treatment (15.23 months versus 8.13 months,P<0.001). However, the overall median PFS was similar in patients treated with either immediate or delayed settings (15.23 months and 16.23 months respectively, P=0.450). There was no significant difference in OS between the two groups. Although patients whose tumors had EGFR mutation showed a longer median PFS compared to those without the mutation in both treatment groups, similar overall PFS was observed between the groups for patients with EGFR mutation (18.75 months and 18.30 months for maintenance and second-line groups, respectively). Conclusions: Immediate gefitinib use may improve PFS for Chinese patients with advanced NSCLC after front-line chemotherapy. However, similar PFS may be achieved by delayed use of gefitinib.

No significant financial relationships to disclose.
Continued high activity of figitumumab (CP-751,871) combination therapy in squamous lung cancer
Authors: Karp D. D. , Novello S. , Cardenal F. , Haluska P. , Blakely L. J. , Garland L. , Paz-Ares L. G. , Dolled-Filhart M. P. , Johnson E. D. , Gualberto A.
Published: August 2020

8072

Background: Figitumumab (CP-751,871) is a fully human, IgG2monoclonal antibody against the insulin-like growth factor type I receptor (IGF-IR). We reported in a randomized phase II study (ASCO 2008), preliminary evidence of high activity of the combination of paclitaxel (T), carboplatin (C) and figitumumab (F) in advanced treatment-naïve NSCLC of squamous cell histology (n=11 pts). A single arm trial extension cohort was conducted to confirm those findings. Methods: Fifty-six pts with non-adenocarcinoma NSCLC were enrolled. Pts received T (200 mg/m2), C (AUC of 6) and F (20 mg/kg) q3weeks for up to 6 cycles; pts with response (PR) or stable disease were eligible to continue F as single agent until disease progression. Statistical hypotheses were 30% (null) versus 50% (response of interest). Protein expression of the IGF-IR in core tumor biopsies was quantified using automated quantitative analysis (AQUA) technology. Results: Pts were 72% male, 28% >70 years old and 91% stage IV. Median number of treatment cycles was 4, with 46% of pts receiving single agent F beyond cycle 4. TCF was well tolerated. The most common all-causality grade 3, 4 CTCAE adverse events were neutropenia (21%), hyperglycemia (14%) and fatigue (14%). Hyperglycemia adverse events almost always occurred within the first treatment cycle and were manageable with standard measures. Responses in squamous pts are currently 25 out of 40 pts according to RECIST, with final response assessment still pending for 7 additional pts (≥53%, p<0.001). One complete response and 7 striking PRs (50–80% tumor size reduction at cycle 2) were observed. Tumor size reductions with F maintenance treatment were also seen in 2 pts. Median progression free survival has not been yet reached at 4 months follow up. A trend (p=0.1) for higher IGF-IR expression in patients responding to TCF was observed in a small data set (n=12). Median tumor IGF-IR expression in pts responding to TCF therapy and non-responders were respectively 6287 and 4131 AQUA scores. Analysis of IGF-IR and other members of the IGF-IR pathway continues. Conclusions: These data further support the activity of figitumumab combination therapy in pts with squamous NSCLC.

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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.