bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognosis of early-onset breast cancer based on BRCA1/2 mutation status in a French population-based cohort
Authors: Bonadona V. , Voirin N. , Sinilnikova O. , Mignotte H. , Bremond A. , Mathevet P. , Romestaing P. , Raudrant D. , Lenoir G. , Lasset C.
Published: March 2020

591

Background: The debate concerning poorer survival for patients with breast cancer (BC) carrying a BRCA1 germline mutation is unresolved, and requires additional data from population-based studies. Methods: We followed 232 women with invasive BC under age 46, ascertained prospectively through a French population-based BC registry, and tested for BRCA1/2 mutations (median follow-up: 82 months). We compared tumour characteristics and survival rates between 21 BRCA1/2 deleterious mutation carriers and 211 non-carriers. Results: As compared to sporadic tumours, BRCA1/2 tumours showed higher grade (p = 0.02), fewer ductal carcinoma in situ (p = 0.02), more frequent medullary histology (p = 0.02), more frequent negative oestrogen and progesterone receptors (p = 0.001 each). At five years, BC-specific survival, metastasis-free survival, ipsilateral recurrence-free survival and contralateral BC-free survival rates for BRCA1/2 mutation carriers were 95.0%, 94.7%, 100% and 90.0% respectively, compared with 89.6%, 78.2%, 88.8% and 94.4% respectively, for non-carriers (not significant). Rates for women carrying only a BRCA1 mutation were 93.3%, 93.3%, 100%, 86.7%, respectively. 76% of BRCA1/2 carriers received chemotherapy. Conclusions: Despite unfavourable tumour features, we found no evidence for poorer short-term survival in BRCA1 mutation carriers compared to non-carriers in this prospective population-based cohort. The high rate of BRCA1 carriers who received chemotherapy for their BC should question the positive impact of this treatment, as suggested by preclinical studies showing increased chemosensitivity of BRCA1-associated tumours.

No significant financial relationships to disclose.
A randomized controlled trial to evaluate the impact of an educational DVD on cancer patients considering participation in a phase I clinical trial
Authors: Strevel E. L. , Newman C. , Pond G. R. , Maclean M. , Siu L. L.
Published: March 2020

6011

Background: Informed consent for phase I trials is controversial; gaps in patient (pt) knowledge regarding the purpose of these studies are central to this debate. This study assessed the impact of viewing an educational DVD on pt knowledge and satisfaction in cancer pts newly referred to a phase I trials clinic. Methods: Prior to physician (MD) appointment, 49 pts were randomly assigned to view either an educational DVD (n = 22) which provided information about phase I trials, or a placebo DVD (n = 27) which described research achievements by local scientists. Upon completion of DVD viewing, pts completed a self-administered questionnaire addressing their understanding of phase I trials (knowledge) and their satisfaction with the DVD (perception). The interviewing MD (n = 8), who was blinded to the intervention, also rated the pt’s understanding of phase I trials upon completion of the clinic appointment. Results: The mean pt age was 56 and 61% were male. Prior to attending the phase I clinic, most pts (86%) had previously heard of clinical trials, but only 49% were aware of phase I trials. Pts who viewed the educational DVD were less likely to believe that the goal of phase I trials is to determine the efficacy of a new drug (p = 0.019), more likely to correctly assess that drugs undergoing phase I evaluations have not been thoroughly studied in humans (p = 0.003), and less likely to believe that phase I drugs have proven activity against human cancers (p = 0.008). More pts who viewed the educational DVD than the placebo DVD agreed/strongly agreed that the DVD provided useful information (p < 0.001), believed that they had a good knowledge of phase I trials (p = 0.031), felt that the DVD helped them decide whether to enter a phase I trial (p = 0.011), and perceived that they would have more questions for their physicians as a result of watching the DVD (p = 0.017). No statistically significant differences in MD satisfaction was observed. Conclusions: Exposure to an educational DVD increased both objective measures of pt knowledge as well as pt satisfaction regarding participation in phase I clinical trials. The educational DVD did not significantly impact MD perception of pt understanding.

No significant financial relationships to disclose.
NCIC CTG MA.17: Tolerability of letrozole among ethnic minority women
Authors: Moy B. , Tu D. , Shepherd L. E. , Pater J. L. , Whelan T. J. , Ingle J. N. , Goss P. E.
Published: March 2020

6018

Background: Disease free survival was significantly improved in women receiving letrozole after standard adjuvant tamoxifen in the MA.17 trial. Based on the results of MA.17 and of other trials of aromatase inhibitors in early stage breast cancer, chronic aromatase inhibitor therapy, in postmenopausal women free of breast cancer recurrence, is now being widely employed. We analyzed the toxicity of letrozole according to ethnic status among women enrolled in MA.17. Methods: The chi-square test was used for comparison of rates of side effects between the two groups, Caucasian vs. ethnic minority (defined as all non-Caucasians). In a subset of women, quality of life (QOL) was assessed by the SF-36 Health Survey. Mean change scores in QOL from baseline were compared between groups for summary measures and domains using the Wilcoxon test. Results: 352 minority women and 4,708 Caucasians were enrolled in MA.17, of which 183 minority women and 2,339 Caucasians were randomized to receive letrozole. Caucasians were older than minority women and had a slightly longer duration of treatment with prior tamoxifen. Tumor size and nodal status were not significantly different between the two groups. In women who received letrozole, minority women had significantly lower incidence of hot flashes (49% vs. 58%; p = 0.02), fatigue (29% vs. 39%; p = 0.005), and arthritis (2% vs. 7%; p = 0.006) compared with Caucasians. Mean QOL change scores of SF-36 domains for women who received letrozole were not different but minority women had better mental health at 6 month assessment (p = 0.02) and worse bodily pain at 12 month assessment (p = 0.046). Conclusions: Minority women tolerated letrozole considerably better than Caucasians in the MA.17 trial. These preliminary findings suggest that minority women respond differently to letrozole in terms of toxicity. Recent demonstration of genotypic variations in the aromatase gene in different ethnic groups plus likely pharmacogenomic differences suggests that further research is needed to clarify the clinical outcomes of aromatase inhibition in women of diverse ethnicities. Future research strategies should focus on examining in vivo genotype-phenotype correlations to determine the effects of genetic variation on response to anticancer therapy and on toxicities and end-organ effects.

[Table: see text]
Predictors of complications following prostate brachytherapy
Authors: Chen A. B. , D’Amico A. V. , Neville B. A. , Earle C. C.
Published: March 2020

6021

Background: Prior studies on complications from prostate brachytherapy have reported on single institution experiences. We assessed the prevalence and predictors of complications following brachytherapy for prostate cancer on a population basis. Methods: We analyzed the claims of Medicare-enrolled men over age 65 living in SEER surveillance areas diagnosed with locoregional prostate cancer from 1991–1999 who underwent brachytherapy as initial treatment. Two-year complications were identified using Medicare diagnosis and procedure codes from the time of brachytherapy through 2001. Results: We identified 6,879 men who had brachytherapy as initial treatment for locoregional prostate cancer, 5,682 of whom had at least two years follow-up. Of these patients, 54.63% had at least one diagnosis or procedure associated with rectal, urinary, or erectile dysfunction, and 14.33% underwent at least one invasive surgical procedure for treating bowel, urinary, or erectile morbidity within two years of brachytherapy. 10.30% of men had procedures for urinary obstruction, 0.18% had procedures for urinary incontinence, 0.77% had rectal procedures, and 4.08% had invasive procedures for erectile dysfunction. Predictors of two-year complication procedures on multivariable analysis are shown in the Table . Conclusions: A significant proportion of men have diagnoses associated with rectal, urinary, or erectile morbidity following prostate brachytherapy. Though procedures for urinary obstruction are common following brachytherapy, invasive interventions for rectal complications, urinary incontinence, and erectile dysfunction are rare. Procedures for complications following brachytherapy appear to have declined over the 1990s.

[Table: see text]

No significant financial relationships to disclose.
Cost-effectiveness analysis of trastuzumab in the adjuvant setting for treatment of HER2+ breast cancer
Authors: Garrison L. P. , Perez E. A. , Dueck A. , Lalla D. , Paton V. , Lubeck D.
Published: March 2020

6023

Background: The addition of trastuzumab (H) to a standard adjuvant therapy regimen (doxorubicin, cyclophosphamide, and paclitaxel; AC→T) is associated with a 52% reduction in risk (p < 0.0001) of disease recurrence in patients with HER2 positive operable breast cancer (Romond et al, NEJM 2005). A cost-effectiveness analysis was performed to assess the lifetime clinical and economic implications of this important clinical finding. Methods: A Markov model with three health states (disease-free survival [DFS], recurrence, and death) was used to estimate the likely cost-effectiveness (CE) for a 50 yr old woman. Efficacy results from both trials (NCCTG N9831/NSABP B-31) were used through 4 years, and projections of time to recurrence and death were based on the literature (EBCTCG, Lancet 2005). After 4 years, annual transition probabilities to recurrence and death are assumed to be the same in both arms. Cardiotoxicity was higher with H (Perez EA, ASCO 2005). Actual total dose of H was used which was lower than scheduled dose. Incremental costs associated with addition of H to adjuvant therapy were estimated using average wholesale prices, Medicare reimbursement rates and other published data. These costs included testing for HER2 status, drug and administration costs for H, cardiac monitoring, treatment of cardiotoxicity, treatment following recurrence, and end-of-life costs for dying patients. Utility estimates were derived from the literature. Results: Over a lifetime, the cost per quality-adjusted life year gained (QALY; discount rate 3%) is $27,800, with a range of $17,900 to $39,100 under multi-way sensitivity analysis. Projected life expectancy from the Markov model is 3 years longer for H patients (19.4 v 16.4 yrs). Over a 20-year horizon, addition of H to AC→T is estimated to cost an additional $46,300 on average, with an expected gain of 1.28 QALYs-a cost/QALY of $36,100. The key drivers of CE are the cost of treatment and the improvement in DFS. Conclusion: The model projects a cost-utility ratio that is below that of many treatments used for oncology patients. The use of trastuzumab in the adjuvant setting for HER2+ breast cancer is projected to be cost-effective.

[Table: see text]
Patient and surgeon correlates of shared decision making for surgical breast cancer treatment
Authors: Hawley S. , Lantz P. , Salem B. , Fagerlin A. , Janz N. , Morrow M. , Hofer T. , Deapen D. , Liu L. , Schwartz K. , Katz S. J.
Published: March 2020

6031

Background: The choice of surgical breast cancer treatment represents an opportunity for shared decision making (SDM), since both mastectomy and breast conserving surgery are viable options. Yet women vary in their desire for involvement in this decision. Correlates of SDM and/or the level of involvement in breast cancer surgical treatment decision-making are not known. Methods: Breast cancer patients of Detroit and Los Angeles SEER registries were mailed a questionnaire shortly after diagnosis in 2002 (N = 1,800, RR: 77%). Their responses were merged with a surgeon survey (N = 456, RR: 80%) for a dataset of 1,547 patients of 318 surgeons. Surgical treatment decision making was categorized into: 1) surgeon-based; 2) shared; or 3) patient-based. The concordance between a woman’s self-reported actual and desired decisional involvement was categorized as having more, less, or the right amount of involvement. Decision making and concordance were each analyzed as three-level dependent variables using multinomial logistic regression controlling for clustering within surgeons. Independent variables included patient clinical, treatment and demographic factors, surgeon demographic and practice-related factors, and a measure of surgeon-patient communication. Results: 37% of women reported the surgery decision was shared, 25% that it was surgeon-based, and 38% that it was patient-based. Two-thirds experienced the right amount of involvement, while 13% had less and 19% had more. Compared to women who reported a shared decision, those with surgeon-based decision were significantly (p < 0.05) more likely to have male surgeons, and those reporting a patient-based decision were more likely to have received mastectomy vs. breast conserving surgery. Women who were less involved in the surgery decision than they wanted were younger and had less education, while those with more involvement (vs. the right amount) more often had male surgeons. Patient-surgeon communication was associated with decisional involvement. Conclusions: Correlates of SDM and decisional involvement relating to surgical breast cancer treatment differ. Determining patients’ desired role in decision making may as important as achieving a shared decision for evaluating perceived quality of care.

No significant financial relationships to disclose.
Use of health administrative databases in the analysis of waiting times and costs for the diagnosis of non-small cell lung cancer (NSCLC)
Authors: Cheung W. Y. , Butler J. , Kliewer E. , Demers A. , Musto G. , Navaratnam S.
Published: March 2020

6042

Background: Knowledge of waiting times and costs involved in diagnosis will help to define more effective diagnostic services. The use of administrative databases for such health services research provides a large, population-based cohort and permits an accurate calculation of costs. Methods: Patients diagnosed with NSCLC in Manitoba, Canada from 1996 to 2000 were identified by the cancer registry. Information on diagnostic and staging tests, timeline of investigations, physician visits, hospital admissions, and outcomes were obtained from detailed chart review for 472 patients and from the Manitoba Health Administrative Databases for 2,862 patients. Tariff codes for physician services were used to calculate costs. Results: An excellent correlation was observed (range 83.3 to 99.2%) between the chart review and the administrative databases with regards to timelines of imaging studies, physician services, and procedures. However, charts considerably underreported certain services. For instance, only 58% of chest x-rays performed were captured by chart review. Therefore, costs were analyzed using the administrative databases. Waiting times from chest x-ray to chest CT scan and from CT scan to definitive histologic diagnosis were a median of 8 (range 1–25) and 18 (range 3–42) days respectively by administrative databases, and 10 (range 1–31) and 18 (range 6–36) days respectively by chart review. At least 25% of 2862 patients waited more than 55 days from initial suspicion on chest x-ray to arrive at a final diagnosis. The mean cost to reach a lung cancer diagnosis was $7,578 but analysis indicates that there were large variations in costs among patients. The majority of expenses was accounted by hospital admissions and repeated primary care physician visits, while shorter waiting times to diagnosis corresponded with relatively less costs. Conclusions: Since there is an excellent correlation between chart review and administrative databases, the latter can be used in the future for large cohort studies instead of expensive, laborious chart reviews. Despite clinical suspicion, 25% of patients wait more than 8 weeks for a final diagnosis. A centralized diagnostic service may reduce waiting times and costs for diagnosis.

No significant financial relationships to disclose.
Is it cost-effective to add erlotinib to gemcitabine in advanced pancreatic cancer?
Authors: Grubbs S. S. , Grusenmeyer P. A. , Petrelli N. J. , Gralla R. J.
Published: March 2020

6048

Background: Single agent gemcitabine has been considered the standard of care in advanced pancreatic cancer since 1996. A recent 569 patient randomized trial comparing gemcitabine alone with gemcitabine + erlotinib as first line therapy found a small but statistically significant difference in survival (6.0 vs 6.4 months, respectively, p = .028). The impact on survival may be small, but with nearly 33,000 new cases of pancreatic cancer per year, the impact on health care costs with the use of the combined regimen may be large. Using the known survival data and costs, we analyzed the incremental cost-effectiveness of adding erlotinib. Methods: Costs for a six month course of gemcitabine were developed using Medicare reimbursement from the January, 2006 CMS Drug Payment Table and Physician Fee Schedule assuming no change in infusion reimbursement. Since erlotinib is not approved as a Medicare Part B drug, costs were developed from wholesale and retail sources. Drug dosing and schedules were based on the clinical trial protocol leading to approval. Incremental cost effectiveness of adding erlotinib was calculated. Results: Six month course of gemcitabine alone costs $23,493. The addition of erlotinib increases cost by $12,156 wholesale or $16,613 retail. Given an increase of 0.4 months in median survival over gemcitabine alone, the addition of erlotinib costs $364,680 per year of life gained (YLG) wholesale and $498,379/YLG retail. Sensitivity analyses were conducted assuming shorter therapy of 4 and 5 months. In order to be cost effective even at the $100,000/YLG level, six months of erlotinib would have to be reduced to 20% of the current retail cost (lowered to $18.52 per tablet.) Conclusions: Adding erlotinib to gemcitabine does not approach cost effectiveness at even the highest year per life gained parameters. Such impacts on health care costs, especially for very small gains, become more pressing as all health care costs continue to increase.

[Table: see text]

[Table: see text]
Prostate-cancer (CaP) screening decision aid for black men designed to enhance shared decision-making
Authors: Gilligan T. D. , Kennedy M. W. , Olson E. , Gerberick A. , Wilson-Glover A. , Allen J. D.
Published: March 2020

6059

Background: The high CaP incidence and mortality of black men combined with their relatively low rate of CaP screening and their elevated risk of presenting with advanced disease has led to their being identified as a high-priority group for screening. The benefit of screening, however, is uncertain. Most guidelines recommend that men make an individualized screening decision in consultation with their doctor. Motivating and preparing men to actively participate in this difficult decision remains a challenge. This is particularly relevant regarding black Americans given their historical alienation from the health care system. Methods: A CaP screening decision aid designed to promote shared decision-making was tested in 5 small group sessions of black men at community sites in Boston. The decision aid was preceded by a brief didactic presentation on CaP screening. The decision aid included a graphical depiction of all potential major outcomes that may follow a decision for or against screening. Vignettes about the decision-making and outcomes of hypothetical men with different life circumstances and priorities were presented to enhance values clarification by the participants. Endpoints measured before and after the intervention included self efficacy (SE)[Decision Self Efficacy Scale], decisional conflict (DC) [Decisional Conflict Scale], desire for autonomy (DFA) [Control Preferences Scale], and prostate cancer knowledge (PCK) [Prostate Cancer Knowledge and Prostate Cancer Screening Knowledge scales]. Pre- and post-intervention scores were compared using a Wilcoxon Matched-Pairs Signed Rank test. Results: 64 men were accrued over 4 months during 2005. Significant changes were seen in all measures. Average scores improved 16% on SE (p<.001) and 17% on DC (p<.004). DFA increased, with the proportion of men wanting to play a dominant role in health care decisions rising from 62% to 81% (p<.001). PCK more than doubled on both scales (p<.001). Focus groups held after the intervention reinforced these findings. Conclusions: Men were better informed, felt better prepared to actively participate in CaP screening decisions, and wanted to play a stronger role in decisions about their health care following exposure to our decision aid.

No significant financial relationships to disclose.
Axillary lymph node nanometastases are prognostic factors for metastatic relapse in breast cancer patients
Authors: Alberti S. , Querzoli P. , Pedriali M. , Rinaldi R. , Biganzoli E. , Boracchi P. , Piantelli M. , Iacobelli S. , Marubini E. , Nenci I.
Published: March 2020

610

Background: Early breast cancer presents with a remarkable and largely unaccounted for heterogeneity of outcomes. Undetected, microscopic lymph node tumor deposits may account for a significant fraction of this prognostic diversity. Thus, we systematically evaluated the presence of lymph node tumor cell deposits <0.2 mm in diameter [pN0(i+), nanometastases], and analysed their prognostic impact. Methods: Seven hundred and two single institution, consecutive patients with 8 years of median follow-up were studied. To maximize the chances of detecting micro and nanometastases, whole-axilla dissections were analysed. pN0 cases were systematically reevaluated by step sectioning and anti-cytokeratin immunohistochemical analysis of 6676 corresponding dissected lymph nodes. The risk of first adverse events and of distant relapse of bona fide pN0 patients was compared with that of pN0(i+), pN1mi and pN1 cases. Crude cumulative incidence (CCI) curves were used to estimate the cumulative probability of occurrence of adverse events. CCI curves were compared by the Gray’s test. A proportional sub distribution hazard (SDH) regression model was utilized to assess the difference among CCI curves of pN0(i+) versus pN0(i-), and of pN1mi versus pN0(i+). Competing risks were accounted for and regression models were adjusted for established breast cancer prognostic factors, i.e. grading, pathological T stage and age. Proportional SDH assumptions were checked using Schoenfeld-type residuals. Results: A pN0(i+) status was shown to be a strong risk factor for event-free survival (P<0.0005) and for metastatic relapse in both univariate and multivariate analyses accounting for competing risks and adjusted for grading, pathological T stage and age. Conclusions: Our findings demonstrate that nanometastases are an important risk factor in breast cancer. These results support the inclusion of procedures for nanometastasis detection in TNM pathological staging.

No significant financial relationships to disclose.
Use of placebo in cancer medicine: The experience of a National Clinical Trials organization
Authors: Pater J. L. , Parulekar W.
Published: March 2020

6104

Background: The use of placebos in cancer clinical trials requires careful evaluation. Factors that must be considered include the impact of placebo on endpoint measurement, the efficacy of placebo relative to standard of care treatment, patient altruism/acceptance of a non-active intervention and the resulting increase in complexity of study conduct with respect to randomization, drug supply, data management, analysis and the unblinding process. Methods: We reviewed the experience of the National Cancer Institute of Canada Clinical Trials Group with the use of placebo in the randomized phase III setting from 1982–2005. Results: Since 1982, 34 studies were identified that utilized a placebo as part of study design. Data is presented below according to the type of study and date of study activation. The numbers in brackets represent those studies in which placebo was used alone in the control arm. Supportive care studies were the most common type of study employing a placebo as part of study design and constituted almost 50% of our Group’s experience. Therapeutic studies involving placebo were conducted in multiple sites including breast (4), lung (6), myeloma (1), melanoma (1), ovary (1) and pancreas (1). Conclusion: Phase III studies involving a placebo constitute an important part of our clinical trial activity and cross the spectrum of supportive care, therapeutic and prevention trials. The use of placebo in cancer studies may increase due to the relative ease of blinding in studies that evaluate targeted, oral therapies with minimal toxicities as well as the need for unbiased assessment of increasingly used endpoints such as time to progression.

[Table: see text]

No significant financial relationships to disclose.
A cost-effectiveness analysis of surveillance, radiotherapy, and carboplatin in the management of stage I testicular seminoma
Authors: Patrice S. J. , Patrice J. R. , Steinberg J. S. , Zietman A. L. , Smith M. R. , Hayman J. A.
Published: March 2020

6108

Background: Alternative post-orchiectomy management strategies for patients with Stage I Testicular Seminoma (TS) have different costs, recurrence risks, and toxicities. This study compares the cost-effectiveness (CE) of surveillance (SVL), dogleg radiotherapy (DLRT), para-aortic radiotherapy (PART), or one cycle of Carboplatin (CARB) from a societal perspective. Methods: Using TreeAge software, a decision tree with embedded Markov process models was constructed to simulate the natural history of Stage I TS from orchiectomy until death for hypothetical cohorts of 35 year-old men. Recurrence risks, established follow-up guidelines, utilities, direct and indirect costs, and excess mortality and costs attributable to late second cancers were modeled. CE and incremental CE (ICER) ratios were calculated per life-year (LY) and quality-adjusted life year (QALY) using a 3% discount rate; one- and two- way sensitivity analyses were performed. Results: The base case results are shown in the Table . SVL is CE when both recurrence risk is decreased 50% and follow-up costs are reduced 65%. PART is CE when follow-up and indirect costs are reduced 29% while PART second cancer relative risk (RR) is reduced to 1.8. CARB is CE when follow-up and indirect costs are reduced 41%, or the PART relapse risk function is increased 41% while DLRT costs are increased 87%. The model was insensitive to changes in utilities. Conclusions: Despite an assumed increased second cancer risk, DLRT is CE. This is due to the routine use of intensive follow-up for the alternative strategies and the high cost of salvage treatment. PART may become CE if a decrease in second cancer RR is observed without increases in recurrences. SVL should be reserved for those with favorable prognostic factors who can be followed less intensely. At a reasonable willingness-to-pay ceiling CARB is optimal, however, the small differences in effectiveness between the strategies may support decision-making based on costs.

[Table: see text]

No significant financial relationships to disclose.
Dose intensity comparison of African-American and white patients in NSABP breast treatment trials of postoperative doxorubicin and cyclophosphamide
Authors: Wilson J. W. , Thomas C. R. , Mamounas E. P. , Raich P. C. , Lagrange A. , Wolmark N.
Published: March 2020

6111

Background: It has been proposed that ethnic neutropenia in African-American (AA) breast cancer patients leads to lower chemotherapy dose intensity (DI) compared to white (W) patients and hence to increased mortality from the disease [Hershman 2003]. Thomas et al. [2005] confirmed that AA patients in NSABP breast treatment trials had lower WBC and ANC than W counterparts and found that the total amount of chemotherapy received was no different in AA and W patients. The aim of the present study was to extend previous work to determine whether postop doxorubicin (A) and cyclophosphamide (C) DIs (as opposed to total doses) were lower in AA pts enrolled in NSABP breast cancer adjuvant treatment trials. Methods: Pooled data from AA and white (W) pts enrolled in NSABP trials B-15, B-16, B-18 (postop pts only), B-22, B-23, and B-25 (N=10,678 total: 1,040 AA pts and 9,638 W pts) were analyzed. Outcome measures were 1) total A received as a % of the total dose projected on the basis of BSA divided by total days of chemotherapy and 2) corresponding % of C divided by total days of chemotherapy. These quantities were compared in AA and W pts using ANOVA with adjustment for protocol, BMI, G-CSF use, C regimen (600mg/m2 ×4, 1200mg/m2 ×2, 1200mg/m2 ×2, 2400mg/m2 ×2, 2400mg/m2 ×4), and significant pairwise interactions among these variables. Results: After adjustment for the above-listed factors, AA was not a significant predictor of dose intensity for either A or C (p = 0.24 for both comparisons). Conclusions: This retrospective exploratory analysis suggests that despite lower baseline WBC and ANC, AA pts enrolled in these NSABP trials did not receive substantially lower A and C DI than did W pts. Recommending identical dose regimens for AA and W patients in AC-based breast treatment trials is thus most likely clinically reasonable.

No significant financial relationships to disclose.
Risk of cardiac (CD) and pulmonary (PD) death after post-operative radiotherapy (PORT) for non-small cell lung cancer (NSCLC): Analysis of the Surveillance, Epidemiology, and End-Results (SEER) program
Authors: Lally B. E. , Detterbeck F. C. , Thomas C. R. , Machtay M. , Miller A. A. , Oaks T. E. , Petty W. J. , Robbins M. E. , Blackstock A. W.
Published: March 2020

6122

Background: Since radiation treatment planning and delivery techniques have evolved over time, we investigated if the risk of CD and PD after PORT for NSCLC has decreased. Methods: We selected postoperative patients with non-metastatic NSCLC diagnosed in 1980–1995 from the SEER data. To account for peri-operative mortality, patients with survival less than 6 months were excluded. Variables analyzed included age, gender, laterality, disease stage, SEER geographic region, ethnicity/race, and histology. CD and PD were calculated at 10 years and compared for patients diagnosed during 1980–83, 1984–88, 1989–91, and 1992–95. Cox proportional hazards models (CPHM) were used to calculate the hazard of CD and PD. Results: This analysis included 29,093 patients treated with observation (OB) and 8334 patients who received PORT. For the patients treated with OB, the 10 yr mortality rates for CD/PD were 17%/2%, 15%/3%, 15%/3%, and 14%/<0.1% for years of diagnosis of 1980–83, 1984–88, 1989–91, and 1992–95, respectively. For the patients who were treated with PORT, the 10 yr mortality rates for CD/PD were 21%/3%, 21%/4%, 15%/4%, and 14%/<0.1% for years of diagnosis of 1980–83, 1984–88, 1989–91, and 1992–95, respectively. CPHM showed the hazard of CD for patients treated with OB to be significantly decreasing; 1980–83 (HR=1.412; CI=1.257–1.585; p<0.0001), 1984–88 (HR=1.260; CI=1.124–1.413; p<0.0001), 1989–91 (HR=1.180; CI=1.054–1.321; p=0.0042), and 1992–95 (HR=1.00; Ref.). CPHM showed the hazard of CD for patients who received PORT to be significantly decreasing; 1980–83 (HR=1.568; CI=1.222–2.011; p=0.0004), 1984–88 (HR=1.435; CI=1.125–1.830; p=0.0036), 1989–91 (HR=0.992; CI=0.767–1.282; p=0.9504), and 1992–95 (HR=1.00; Ref.). Although PD showed a similar decreasing trend relative to year of diagnosis, CPHM did not demonstrate this to be statistically significant. Conclusions: There was a greater reduction in the CD rate in the PORT group compared to the OB group. While there appeared to be a trend in the reduction of PD, the results were not significant which may be secondary to too few events occurring.

No significant financial relationships to disclose.
A case-control study evaluating differences in resource utilization between diabetic and non-diabetic cancer patients undergoing chemotherapy
Authors: Robertson M. D. , George T. J. , Chang M. , Richardson L. C.
Published: March 2020

6126

Background: Patients with diabetes mellitus (DM) and cancer have been noted to have worse overall and disease-free survival compared to those without DM. However, there is a paucity of data addressing why diabetic cancer patients have worse outcomes. We performed a retrospective case-control study to evaluate cancer patients undergoing chemotherapy comparing persons with and without DM to evaluate differences in resource utilization and mortality. Methods: Using chart review and tumor registry data from January 2001 through December 2003, we identified DM patients 18 years or older, treated with chemotherapy at the Gainesville Veterans Administration Medical Center (GVAMC) for lung, colon, or head and neck cancer. Non-diabetic (Non-DM) controls were matched for age, cancer type and stage. A comorbidity score was calculated based on a previously validated measurement scale, Adult Comorbidity Evaluation 27 (ACE-27). The primary outcome measure was the number of inpatient hospital days in the first year after diagnosis. Secondary outcome measures included the total number of outpatient visits, emergency room (ER) visits, infusion room visits for chemotherapy, blood transfusions, home health consults, telephone calls, and mortality. Results: A total of 42 DM cases and 42 non-DM controls were identified who had undergone similar treatments with radiation and surgery. The DM patients had higher comorbidity ACE 27 scores when corrected for the cancer being treated, median 3.0 versus 2.0, p < 0.005. The table summarizes the results. Mortality was the same (15) for both the DM and non-DM patients at one year. Conclusions: Cancer patients with DM undergoing chemotherapy have significantly more comorbidities and utilize more outpatient visits compared to non-DM. However, all other measures of resource utilization and mortality appear similar. Further studies to identify causes of increased utilization should be done.

[Table: see text]

No significant financial relationships to disclose.
Utilization of positron emission tomography scans (PET) in the management of NSCLC at a center with limited access to this imaging modality
Authors: Nair B. P. , Safar A. M.
Published: March 2020

6140

Background: PET is recommended as an important diagnostic aid in the initial evaluation of patients with lung cancer, according to the NCCN guidelines. The aim of this study is to estimate the proportion of NSCLC patients receiving PET, its impact on staging, and its utilization by different treating specialties, in a facility with limited access to PET. This is a situation comparable to several community medical centers. This study was done at the Veterans Hospital, Little Rock (VALR), where the requested PET scans were done at an outside facility, due to its unavailability within this center. Methods: All patients with NSCLC who were diagnosed or treated at VALR between 01/01/03 and 06/30/05 were retrospectively identified from the tumor registry, and details of PET were obtained. Subsequently electronic patient records at VALR were reviewed and the best estimate of pre-PET and post-PET stage was made. The details of the requesting specialty were also obtained. Then frequency distributions relevant to the aims of the study were calculated. Results: 444 patients with diagnosis of NSCLC were identified in this time period, of which 48 (10.8%) had PET scans. Overall 10 (21%) patients were down staged and 4 (8.3%) patients were upstaged. PET helped establish stage among 13 of 15 patients with unknown stage. Details are provided in the table . The number of PET scans requested by treating specialties are as follows: medical oncology 44% (21), pulmonary 40% (19), cardiothoracic surgery 13% (6), and others 3% (2). Conclusions: In this study 10.8% of patients with NSCLC had PET. There was establishment of, or change in stage among 27 (56%) patients. These numbers are comparable to studies from larger centers with ready availability to PET, reflecting its adequate utilization in this setting with limited access. Medical oncology and pulmonary services initiated majority of the PET requests, possibly because of their involvement in the early diagnostic work-up in this patient population.

[Table: see text]

No significant financial relationships to disclose.
How conversations about adjuvant hormonal therapy differ from ‘typical‘ oncology discussions: Results of an observational linguistic study
Authors: Davidson B. , Vogel V. , Wickerham L.
Published: March 2020

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Background: Adjuvant hormonal therapy in breast cancer presents a conversational challenge for oncologists. Oral medications are a relatively new therapeutic paradigm, and many aspects of typical oncology communication, e.g., risk-benefit presentation, goal of therapy, and the role of patient in selecting/continuing therapy, require a different approach in this setting. An observational linguistic study was undertaken to capture how oncologists and patients discuss adjuvant therapy, and to develop recommendations to improve communication. Methods: Letters of invitation were mailed to 800+ community-based oncologists; of these, 14 met the screening criteria and agreed to participate in this study. 28 postmenopausal, early breast cancer patients on or initiating hormonal therapy were recorded during their regularly scheduled visits. Results: Adjuvant hormonal therapy discussions differ from infusional chemotherapy-focused oncology discussions in several ways: Selection of therapy is based on more than efficacy (e.g., cost, side effects); Chance of recurrence is discussed directly, without significant hedging; Disease name (“cancer”) is discussed openly–the word “cancer” is notably absent from other types of oncology discussions; Visits are routine–patients’ lives are no longer “on hold” (unlike other treatment discussions, where chemotherapy is assumed to be at the center of the patient’s life); Time between visits often moves from every three months to every six months after being on hormonal therapy for a year (unlike other therapies, where patients are seen frequently). Conclusions: Analysis of conversations shows that these patients are seen as, in some way, “cured” (goal of therapy is to prevent recurrence) and that patients are “given their lives back.” The conversational frame displays a lack of urgency and emotion, similar to that of discussions of dyslipidemia management and not like other chemotherapy discussions where the emotional content is very high. New models of therapy require new conversational approaches, e.g., where issues like adherence should be addressed directly, and longer-term therapeutic goals take on primary importance.

[Table: see text]
Development of a model emergency oncology response system (EORS): The California oncology emergency master plan (COEMP)
Authors: Moss R. , Yu P. , Presant C. , Gonzalez J. , Lamb M. , Tucker S.
Published: March 2020

6142

Background: Hurricane Katrina displaced patients (PT) and physicians (MD). Time & resources were needed to match displaced PT with oncology (ONC) practices (PRC) for ongoing care. Disruption of care can be life-threatening to ONC PT who need to adhere to schedules & monitoring. California (CA) is particular risk for natural disaster. In order to better support PT in a future emergency (E) MOASC & ANCO created a model EORS with pilot implementation of select elements. Methods: MOASC & ANCO prepared a multi-component COEMP. Joint calls & meetings yielded a draft EORS approved by both society boards. Initial & long-term funding is expected via granting mechanisms. Pilot implementation of specific elements began in 11/2005. Results: Goals of the COEMP are: Establish dedicated E ONC MD network; Create a voluntary ONC-specific PT medical record (MR) template & secure data repository; Create & test a functional E MD responder system for CA ONC MD; Develop liaison with relief providers (Homeland Security, FEMA, Red Cross); Strengthen existing role with Bio-Pharma (BP) for delivery of medicine (Rx) to displaced PT and PRC; Develop specific educational materials for the EORS (PT, MDs, Insurers, BP); Create & distribute an EORS “PT Wallet Card” with PT national digital record (NDR) and E responder contacts. To prioritize components of the COEMP, a needs assessment, reviewing past E experience, response, and current capacity, has been initiated. The specific active components of the EORS include: 1-E ONC MD support network: ONC MDs have been invited to volunteer via email and at regional meetings. 2-Secure PT MR repository: MDs and PT will coordinate relevant MR, insurance, and E contact data, in locations (home of PT, w/relatives, NDR). 3-E coordinator MDs & staff will respond to E calls from PT/MD via phone & email. 4-Open dialogue with BP for E access to Rx for displaced PT. 5-Educational & training for PRC and PT in printed & electronic form. Conclusions: COEMP provides an initial E model for ONC. It may be applicable for state societies or national ONC groups. At ASCO 2006, MDs will be invited to participate and expand COEMP capabilities. Although we hope COEMP/EORS need never be used, its development will enable ONC practices to be more prepared for loco-regional E.

No significant financial relationships to disclose.
Clinical activity and safety of the histone deacetylase inhibitor MGCD0103: Results of a phase I study in patients with leukemia or myelodysplastic syndromes (MDS)
Authors: Garcia-Manero G. , Minden M. , Estrov Z. , Verstovsek S. , Newsome W. M. , Reid G. , Besterman J. , Li Z. , Pearce L. , Martell R.
Published: March 2020

6500

Background: MGCD0103 is a novel inhibitor of human histone deacetylases (HDACs), with selectivity for the cancer-associated isoforms of class I HDACs. Deacetylation of histones by HDACs is postulated to inactivate tumour suppressor genes leading to neoplastic transformation, and therefore inhibition of this enzyme may result in antineoplastic activity. Methods: To study the safety and activity of MGCD0103, we have developed a phase I open-label dose escalation study of MGCD0103 administered orally, three-times weekly in patients with leukemia or MDS, with the primary endpoints being the determination of the maximum tolerated dose (MTD) and the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of MGCD0103. Eligibility criteria included appropriate performance status and renal and hepatic functions. Patients with relapsed/refractory leukemia or MDS and older patients with untreated AML/MDS were eligible. Results: Twenty patients have been enrolled at four dose levels (20, 40, 80 and 60 mg/m2) so far. Their characteristics are: median age 60 years (range 33–76); the majority of patients so far treated have AML; median number of prior therapies is 1 (range 0–3). Most patients had complex cytogenetics. MGCD0103 has been well tolerated at doses below 80 mg/m2. The MTD has been reached, with 3 out of 4 patients at a dose of 80 mg/m2 developing grade 3 toxicity, mainly fatigue, nausea, vomiting or diarrhea. Grade 2 toxicities include anorexia, constipation, dehydration. The median number of courses is 1 (range 1 to 6). As of January 2006, 7 patients are on study. PK evaluations show dose-dependent exposure. Analysis of peripheral blood cell HDAC activity indicates that HDAC inhibition occurs in all patients in a dose-dependent manner. Two patients with multiple relapsed/refractory acute myelogenous leukemia, and one with MDS have achieved a complete marrow response (blasts less than 6%). Of importance, maximal HDAC inhibition was observed in those patients at the time of best response. Conclusions: Single-agent MGCD0103 has clinical activity and is well tolerated at doses below 80 mg/m2 orally three times a week in patients with advanced leukemia.

No significant financial relationships to disclose.
High expression of the transcription factor ERG predicts unfavorable outcome in acute T-lymphoblastic leukemia (T-ALL) in adults
Authors: Baldus C. D. , Burmeister T. , Martus P. , Schwartz S. , Goekbuget N. , Bloomfield C. D. , Hoelzer D. , Hofmann W. K. , Thiel E.
Published: March 2020

6505

Background: In adult T-ALL long-term survival remains limited to 32–46%. Transcription factors are frequently targeted by chromosomal translocations resulting in disruption of hematopoietic proliferation and differentiation. The oncogenic ETS transcription factor ERG is expressed during early T-cell development and shut off once T-cell commitment is complete. We hypothesized that due to its specific involvement in T-cell maturation and oncogenic potential, ERG might contribute to leukemogenesis. Thus we have determined the prognostic impact of ERG expression in T-ALL. Patients and Methods: ERG mRNA expression was analyzed by real-time RT-PCR in pretreatment marrow samples of 105 adults with T-ALL treated on German ALL protocols. Patients (pts) were dichotomized at ERG’s median expression into low (n=52) and high (n=53) expressers. HOX11 and HOX11L2 expression was determined by real-time RT-PCR. Immunophenotyping was performed differentiating T-ALL into 3 subtypes: pre-T (CD2-), thymic (CD1a+), and mature (sCD3+). Results: High ERG expression was associated with a higher relapse rate (45%) compared to pts with low ERG expression (20%; P=0.01). High ERG expressers compared to low ERG expressers had an inferior overall survival (OS, P=0.02; 5-year OS: high ERG 26% vs low ERG 58%) and relapse-free survival (RFS, P=0.003; 5-year RFS: high ERG 34% vs low ERG 72%). On multivariable analysis high ERG expression (P=0.005), immunophenotypic subgroups (pre-T vs mature vs thymic; overall P=0.04), HOX11L2 positivity (P=0.055) and absence of HOX11 expression (P=0.017) were independent adverse risk factors predicting RFS. Patients with high ERG expression had a hazard ratio (HR) for relapse of 3.2. Within the good prognostic subgroup of thymic T-ALL (n=57) high ERG (HR 4.1; P=0.02) and presence of HOX11L2 (HR 6.6; P=0.008) were independent adverse factors for RFS. Conclusion: High expression of the oncogene ERG is an adverse factor in adult T-ALL. Within thymic T-ALL otherwise classified as standard risk, high ERG expression identified pts that were more than four times likely to fail long-term RFS. The prognostic impact of ERG may assist treatment stratification and suggest the need of more intensive regimens for these high risk thymic T-ALL pts.

No significant financial relationships to disclose.