bluuebunny/crossref_metadata_2025 huggingface dataset:
The quality of phase I trial (P1T) abstracts submitted to ASCO meetings
Authors: Strevel E. L. , Chau N. , Pond G. R. , Murgo A. J. , Ivy S. P. , Siu L. L.
Published: March 2020

6532

Background: Conference abstracts of P1T communicate important information of anticancer drug development. Our objectives were to determine elements considered by experts as essential for good P1T abstract reporting, to assess the quality of P1T abstracts submitted to ASCO meetings, and to propose guidelines for future reporting. Methods: Elements important for P1T abstract reporting were determined by a survey of experts in developmental therapeutics, and a scoring system for abstract quality was generated. All P1T abstracts published in ASCO Proceedings from 2002–2006 were reviewed, and a quality score was assigned. Results: An electronic survey was sent twice to 69 experts, with a response rate of 39% (27/69). Characteristics of the 27 experts were: average age = 48; male = 74%, USA:Europe:Canada = 78%:15%:7%; 89% had 10+ years experience in drug development; 93% from academic institutions versus 7% from governmental agencies; 56% currently involved in clinical research versus 44% in translational research. Experts were asked to rate each of 37 elements using a five-point Like rt scale, and elements with average expert ratings over 3.75 were included in the final quality score calculations. A total of 920 P1T abstracts over 5 years were reviewed. A positive and linear association was observed between average expert rating of the elements and proportion of P1T abstracts that included those elements (Spearman correlation coefficient, ρ=0.65). The median quality score for all 920 abstracts was 65% (range 26%–95%, SD 12.6%). Deficiencies existed in abstract reporting; for instance, dose-limiting toxicity was described in only 63% of abstracts, while recommended dose or maximum tolerated dose was reported in only 38%. A significant association between year of presentation was found (ρ=0.36, P<0.001), with later years possessing better quality scores. The quality score was also statistically significant as a predictor of type of presentation (odds ratio 0.20, 95% CI 0.08–0.54, P=0.002), with oral presentations having the highest scores. Conclusion: The quality of P1T abstract reporting at ASCO has improved over time, although there is room for optimization. The quality of P1T abstract reporting may be enhanced using guidelines derived from our expert consensus.

No significant financial relationships to disclose.
To determine the cost-effectiveness of pemetrexed (PEM) compared to current standards of care in 2nd-line advanced non-small cell lung cancer (NSCLC) from the UK National Health Service (NHS) perspective
Authors: Bhalla S. , Hibbert C. , Watkins J. , Beard S. , Cetty M. , Arellano J.
Published: March 2020

6540

Objective: To assess the clinical and cost-effectiveness of pemetrexed (PEM) compared with current standards of care (SOC) in 2nd-line advanced NSCLC from a UK perspective. The SOC selected for the evaluation were: (i) docetaxel (DOC) as it is the standard active therapy in the UK and is recommended by the National Institute for Health and Clinical Excellence (NICE) and (ii) best supportive care (BSC) as the majority patients in the UK who fail 1st-line therapy do not receive further chemotherapy. Methods: The analytic technique used was a cost-utility analysis (CUA) in the form of a Markov model. Utilities were generated from 100 members of the general public, considering tumor response status and toxicity, in accordance with the standard NICE appraisal methodology. Clinical inputs were derived from a pooled analysis phase III clinical trial data. Costs were taken from the British National Formulary and UK national databases. The incremental cost-effectiveness ratios (ICERs) are presented for both life-years gained (LYG) and quality-adjusted life- years (QALY) gained. Conclusions: The incremental cost per LY and cost per QALY for pemetrexed in 2nd-line NSCLC are below £20,000, compared to docetaxel and BSC. Based on its survival and toxicity benefits PEM is a cost-effective option in within the UK.

No significant financial relationships to disclose.

[Table: see text]
Evaluation of number of target lesions to analyze in time to progression by RECIST
Authors: Gonen M. , Schwartz L. , Ford R.
Published: March 2020

6549

Background: RECIST criteria were designed to evaluated tumor shrinkage and response to therapy by measurement of multiple target lesions, evaluation of non target and new lesions. There is considerable controversy surrounding the optimal number of lesions to assess response, with RECIST requiring the measurement of up to 10 target lesions. These guidelines were set up to evaluate the endpoint of best overall response. Increasingly, time to progression has become an important endpoint in oncology trials. We evaluated the optimal number of lesions to measure to accurately and reproducibly assess time to progression. Methods: We evaluated target lesions metastases in 105 patients enrolled on a Phase III clinical trial. All patients underwent CT at baseline and standard follow up scans until progression. Target lesions were measured unidimensionally and response was assessed according to RECIST by 2 independent Radiologists. A total of 519 target lesions were assessed. Response was calculated according to the rules of target lesions (up to 10) by RECIST, utilizing the 2 largest lesions and randomly selecting 2 target lesions. Results: Using the 2 largest lesions, time to progression was concordant in 83% of cases. The 2 Radiologists determined the two same largest lesions in 89% of cases. Since the determination of the largest or the same target lesions is not always possible or performed, a random selection of 2 target lesions demonstrated a 76% concordance in the time to progression. Conclusions: Measurement of time to progression may have a greater degree of variability than measurement of best overall response and therefore measurement of minimal selected lesions will lead to a great variability in response assessment.

No significant financial relationships to disclose.
Sociodemographic factors influencing Breslow thickness at diagnosis for patients with melanoma
Authors: Stitzenberg K. B. , Thomas N. E. , Berwick M. , Anton-Culver H. , Mujumdar U. J. , Millikan R. C.
Published: March 2020

6552

Background: In previous work, we demonstrated that Breslow thickness at diagnosis is significantly related to distance to provider for patients with melanoma in North Carolina (NC). Expanding the study population to include patients in New Jersey (NJ) and southern California (CA), we hypothesize that distance to provider is an effective measure of access to melanoma care regardless of geographic region. Methods: An IRB-approved secondary data analysis was performed of all incident cases of invasive cutaneous melanoma in 2000 from 3 population-based ascertainment areas (CA, NC, NJ). Patients and providers were geocoded to street address; Euclidian distances between patients and providers were calculated. The outcome variable, Breslow thickness at diagnosis, was logged for analysis. Simple and multiple linear regression were used to test associations between Breslow thickness and multiple sociodemographic factors. Results: Of 1,408 eligible cases, 16% were excluded for missing Breslow data. Median Breslow thickness was 0.6 mm (range 0.01–30.0 mm). Median distance to provider was 7 miles (range 0–372 miles). There was no significant difference in Breslow between the 3 geographic regions. Males had on average 15.5% thicker tumors than females, p=0.009. Patients 51–80 years old had 15.3% thicker tumors than patients =50, p=0.015, and those >80 had 64.3% thicker tumors than patients =50, p<0.001. For all patients, Breslow thickness increased only 2% for each 10 mile increase in distance, p=0.047. However, when limited to patients from rural areas, each 10 mile increase in distance corresponded to an 8% increase in Breslow, p<0.001. Meanwhile, Breslow was not associated with any area-based measures of rurality or provider supply. Each 1% increase in poverty rate corresponded to a 1% increase in Breslow, p=0.036. Conclusion: Breslow thickness at diagnosis is strongly correlated with distance to provider, especially for patients from rural areas. Distance to provider is a better measure of access to melanoma care than area-based measures of rurality.

No significant financial relationships to disclose.
Racial differences in the perception of lung cancer: Data from the 2005 Health Information National Trends Survey (HINTS)
Authors: Lathan C. S. , Okechukwu C. , Drake B. F. , Bennett G.
Published: March 2020

6556

Background: Black men have the highest rates of lung cancer incidence and mortality in the US, and yet continue to obtain treatment at lower rates than White patients. Racial differences in the perception of lung cancer in the population could contribute to racial disparities in seeking timely treatment. Methods: Data are from the 2005 HINTS survey. Sample design was random digit dialing of listed telephone exchanges in US. Complete interviews were conducted on 5491 adults, of which 1872 respondents were assigned to receive questions pertaining to lung cancer. All analyses were conducted on this subset of respondents. SAS callable SUDAAN was used to calculate χ2 tests and perform logistic regression analyses to model racial differences in perceptions of lung cancer. All estimates were weighted to be nationally representative of US population; jack knife weighting method was used for parameter estimation. Results: Black and White patients shared many of the same beliefs about lung cancer mortality, and etiology. African Americans were more likely than Whites to agree that its hard to follow recommendations about preventing lung cancer (OR 2.05 1.19–3.53 95% CI), to avoid evaluation for lung cancer due to fear of having the disease (OR 3.32 1.84–5.98 95% CI), and to believe that patients with lung cancer would have pain or other symptoms before diagnosis (OR 2.20 1.27–3.79 95% CI). Conclusions: African Americans are more likely to hold beliefs about lung cancer that could interfere with prevention and treatment of lung cancer.

No significant financial relationships to disclose.

[Table: see text]
An automated practice-based intervention for case management of abnormal mammograms
Authors: Eberl M. M. , Fox C. H. , Broffman G. , Pomerantz J. , Serghany J. , Reinhardt M. , Watroba N. , Edge S. B.
Published: March 2020

6563

Background: Failure to obtain follow-up (f/u) of abnormal mammograms may delay cancer diagnosis and impact outcome; studies show up to 20% of women do not get recommended f/u. Our group previously established that administrative claims linked to medical records accurately identify care for management of abnormal mammograms. We are testing a case management system linking claims data to mammogram information to assist physicians in assuring appropriate f/u for abnormal mammograms. Methods: Electronic medical records in a staff model practice affiliated with a single payer are scanned to identify the BI-RADS code for all mammograms. The practice performs about 8,000 mammograms with about 500 abnormal mammograms annually. Physicians are notified of each abnormal mammogram and provided with a standardized care pathway for management. For each BI-RADS 0, 3, 4 or 5 mammogram, claims are searched for f/u breast procedures (imaging, biopsy, surgery). If recommended f/u (additional imaging for BI-RADS 0, biopsy by 2 months for BI-RADS 4 and 5, f/u imaging by 8 months for BI-RADS 3) is not observed, the ordering physician is alerted. Results: From 01/01/2001 to 12/31/2003, we observed that among women eligible for f/u, 189 (16%) did not receive BI-RADS recommended f/u care. In the prospective intervention from 1/1/06 - 6/30/06, 166 BI-RADS 0, 21 BI-RADS 4, and 3 BI-RADS 5 mammograms had 98.2%, 76.2%, and 100% appropriate f/u, respectively. From the alerts, all but one patient who refused biopsy received appropriate care. Conclusions: A practice intervention utilizing BI- RADS data linked to claims accurately identified missed f/u in a time frame when appropriate care can be delivered. This practice-based intervention has potential to improve the management of other cancers and chronic diseases. This intervention is being expanded on a community wide level.

No significant financial relationships to disclose.
Breast cancer diagnosis and treatment in a safety net setting: Differences between insured and uninsured patients
Authors: Farrell N. J. , Bradley C. J. , Schickle L. M.
Published: March 2020

6566

Background: Despite the safety net system and many other means of providing free or low cost care to women with breast cancer, disparities in health outcomes between uninsured and insured women with breast cancer exist. In this study, we evaluate the role of health insurance on breast cancer treatments at a large safety net hospital system. Methods: From the patient population at the Massey Cancer Center at Virginia Commonwealth University Health Care System (a large regional safety net provider), we selected women ages 21 to 64 diagnosed with breast cancer between January 1999 and March 2006 (n=1,381). We used billing records to identify health insurance status of these patients. First, we compared the stage of disease and tumor size at diagnosis for women with and without insurance. Next, we compared the number of days between diagnosis and surgery and the number of days between surgery and chemotherapy initiation. Finally, we estimated the number of days it took these groups of women to complete a common adjuvant chemotherapy regimen of doxorubicin plus cyclophosphamide (AC) or doxorubicin plus cyclophosphamide followed by paclitaxel (ACT). Results: Our analysis shows that women without insurance were more likely to have more advanced cancers and correspondingly larger tumors. Uninsured women experienced considerable delays from the date of diagnosis to surgery and from surgery to chemotherapy initiation compared with insured women (21.5 and 22 days longer, respectively). Uninsured women also took significantly longer to complete adjuvant chemotherapy regimens relative to insured women (4 and 26 days for AC and ACT, respectively). Conclusions: To understand the disparities that exist in breast cancer outcomes among women with and without health insurance, we must understand the different experiences these groups of women have with treatment. In this study, uninsured women had more advanced cancers, and experienced considerable delays receiving and completing treatment relative to insured women. Our study demonstrates the value of health insurance in the timely provision of health care even in a safety net setting where care is guaranteed.

No significant financial relationships to disclose.
Costs of administration of intravenous (IV) therapies in early versus late stage breast cancer in a US population
Authors: Kruse G. B. , Amonkar M. M. , Skonieczny D. , Smith G. L.
Published: March 2020

6588

Background: There are significant costs associated with IV administration of cancer drugs ranging from adverse events associated with the administration to the need for specialized equipment, supplies and personnel time. This study utilized a novel provider-payer contract database to compare the cost components of providing IV therapy to women with early and late stage breast cancer. Methods: Women diagnosed with breast cancer (ICD-9 code 174) between 01/01/2003 and 05/31/2006 and receiving IV monotherapy were identified from an administrative claims database of >60 multi-specialty medical practices/clinics (additional ICD-9 codes 196–198 used to identify late stage breast cancer). Costs were estimated on a per IV administration visit basis using the allowable amount for a claim which closely represents the actual amount paid to providers. Published literature was used to categorize the various billable cost components. Results: 1,393 early and 828 late stage breast cancer patients receiving any of 11 IV breast cancer drugs were identified. The costs breakdown by category for all drugs and for the 2 most commonly used drugs, per IV administration visit, is presented in the table . Conclusions: Costs associated with administration of IV therapies and other visit-related services constituted more than 36% of total costs for early stage and 41% of total costs for late stage breast cancer patients. These costs represent a significant cost burden to payers. Maximization of valuable resources could be effected by increased use of effective oral therapies for treatment of breast cancer.

[Table: see text] [Table: see text]
Measuring clinically significant chemotherapy-related toxicities using Medicare claims from CALGB breast and lung cancer trial participants
Authors: Lamont E. B. , Herndon J. E. , Weeks J. C. , Henderson I. C. , Lilenbaum R. , Schilsky R. L. , Christakis N. A.
Published: March 2020

6595

Background: Because the elderly are numerically underrepresented in cancer clinical trials, the benefits and toxicities of cancer therapies in the general population of elderly patients is not known. Nevertheless, clinicians need such information. A solution may be found in analyses of observational data. Specific Aim: We performed a criterion validation study to determine the accuracy with which observational Medicare claims data measure clinically significant chemotherapy-related toxicities in elderly Medicare beneficiaries with cancer. Methods: We created a cohort of 175 elderly clinical trial patients treated on two Cancer and Leukemia Group B (CALGB) trials (i.e., 9,344 adjuvant breast and 9,730 advanced lung cancer trials) and merged participants’ CALGB data with their Centers for Medicare and Medicaid Services (CMS) data. From CALGB data, we identified all grade III/IV toxicities with a frequency of ≥3%. We reviewed diagnostic and procedure codes from CMS coding manuals, developed initial algorithms to measure the toxicities and then finalized the algorithms after empiric review of individual patients’ actual CMS codes incurred during the observation period (i.e., date of first trial treatment through 90 days following last trial treatment). We compared results of each of our CMS toxicity algorithms to gold-standard of CALGB grade III/IV toxicity information in order to calculate the CMS algorithms’ test characteristics. Results: The following 15 grade III /IV chemotherapy-related toxicities occurred in ≥3% of the 175 patients: white blood cell, hemoglobin, platelets, anorexia, nausea, vomiting, diarrhea, stomatitis, sensory neuropathy, motor neuropathy, motor or sensory neuropathy, dyspnea, hyperglycemia, infection, and malaise. Of these, only the CMS-based algorithm measuring ‘grade III/IV vomiting‘ had a sensitivity, specificity, and area under the ROC of ≥ 80%. Conclusions: The results of this preliminary study suggest that CMS claims data may be of only limited value in measuring clinically significant chemotherapy- related toxicities in elderly Medicare beneficiaries with cancer. Future research will focus on confirming these findings in a larger and more diverse patient sample.

No significant financial relationships to disclose.
Outcomes for hematologic malignancies in the Nurses’ Health Study (NHS) as compared to the Surveillance, Epidemiology, and End Results (SEER) program
Authors: Abel G. A. , Bertrand K. A. , Earle C. C. , Laden F.
Published: March 2020

6599

Background: Health literacy, often defined as the degree to which an individual can obtain and understand information needed to make appropriate health decisions, may lead to a decreased incidence and improved mortality for some cancers by promoting risk factor modification and adherence to treatment. As a result, nurses, who presumably possess a higher level of health literacy and access to care than the general population, might be expected to manifest a lower incidence of and better survival for the hematologic malignancies. Methods: We assessed the incidence, all-cause, and cause-specific mortality for Hodgkin's disease (HD), non-Hodgkin's lymphoma (NHL), multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) in the NHS, an ongoing cohort study of 121,700 female registered nurses aged 30–55 years at entry who have been followed for 30 years. We compared these outcomes to those in the SEER program of the National Cancer Institute, matching for age and race. Results: In over 2.5 million person-years, the incidence of HD in the NHS was the same as in SEER. The incidence of NHL, CLL and MM was slightly increased. All-cause mortality was better in the NHS when compared to SEER for HD (HR= 0.62, 95% CI: [0.38, 1.0]) and NHL (HR= 0.81, 95% CI: [0.71, 0.91]). There were no differences in cause-specific mortality, except for MM, which was worse in the NHS (HR= 1.27, 95% CI: [1.07, 1.52]). Conclusion: The incidence of hematologic malignancy is not reduced in nurses, possibly because preventable risk factors for these cancers have yet to be elucidated. To the contrary, the slight increase in incidence for NHL, MM and CLL may be due to higher levels of overall health vigilance and/or occupational exposures. The fact that cancer-related mortality is similar for nurses as compared to age and race-matched SEER controls casts doubt on the roles of health literacy and access to care in improving survival for these disorders.

No significant financial relationships to disclose.

[Table: see text]
Nomograms to predict serious adverse events (SAEs) in patients (pts) enrolled in phase II clinical trials of molecularly targeted agents (MTAs)
Authors: Pond G. R. , Siu L. L. , Moore M. J. , Oza A. M. , Hirte H. , Winquist E. , Goss G. , Hudes G. , Degendorfer P. , Townsley C. A.
Published: March 2020

6601

Background: The likelihood of experiencing a SAE in clinical trials with a MTA is of interest for clinicians discussing treatment options. Adverse event data from clinical trials in the Princess Margaret Hospital Phase II Consortium [PMH2C] database were analyzed to address this question. Methods: All pts in the PMH2C database treated at the phase II dose level with either a MTA alone or in combination regimens since 2001 were included. Generalised estimating equations were used to construct optimal regression models predicting the increased/decreased odds of a SAE of all causalities (defined as a grade 3+ non-hematologic adverse event, or a grade 4+ hematologic adverse event) during the first cycle of treatment relative to a ‘reference’ pt. Nomograms were constructed to ease interpretation and internal validation explored using bootstrapping on trials larger than 35 pts. Results: 576 pts (median age=60, 55% male, ECOG PS 0:1:2=259:284:35) were accrued to 42 studies. In order of statistical significance, higher ECOG PS, increased LDH, decreased albumin, increased Charlson score, increased number of target lesions, not having prior radiotherapy and decreased age were predictive of increased odds of cycle 1 SAE. As an example, a 56-year old patient with ECOG 2, Charlson score=0, 5 target lesions, LDH=1.70x upper limit of normal [ULN], albumin=0.84xULN and no prior radiation would have ∼3 times increased odds of a SAE in cycle 1, compared to a 63-year old with ECOG 1, Charlson score=0, 1 target lesion, LDH=0.76xULN, albumin=0.68xULN and no prior radiation. Internal validation of the 4 largest studies indicated moderate-good accuracy (estimated area under the receiver operating characteristic curve = 0.57–0.86). Conclusions: A nomogram was produced allowing estimation of the increased odds of a SAE during cycle 1 of therapy in a phase II trial setting. Actual risk can then be further estimated by incorporating clinical judgment of risks for an average pt when given a particular MTA. This nomogram can potentially improve patient knowledge, risk estimates and the decision-making process. External validation of the model is still necessary to adequately assess model reliability.

No significant financial relationships to disclose.
Colony stimulating factor use and outcomes for breast, lung, and colorectal cancer patients in Washington State
Authors: Ramsey S. D. , Sullivan S. D. , Malin J. , Blough D. K. , Clarke L. , McCune J. S.
Published: March 2020

6616

Background: Guidelines recommend colony stimulating factor (CSF) primary prophylaxis (PP) with chemotherapy if febrile neutropenia risk (FN) is =20%. Use of and outcomes for persons receiving CSF in clinical practice are relatively unknown. Methods: Using claims for Medicare and Medicaid enrollees linked to the Puget Sound SEER registry, breast (BCa), lung (LCa) and colorectal cancer (CRCa) patients diagnosed 2002–04 who received chemotherapy were categorized as: CSF at the start of chemotherapy (PP); other CSF; no CSF. Logistic regression was used to determine predictors of CSF PP and hospitalization for FN, controlling for cancer stage, age, sex, race, chemotherapy FN risk (from the National Comprehensive Cancer Network), radiation therapy, CSF use, health insurance, surgery =30 days of chemotherapy. Results: 364 BCa, 908 LCa, and 452 CRCa patients received chemotherapy. 43% of BCa, 30% of LCa, and 15% of CRCa patients received CSF. Only 9%, 6%, and 0.6% of patients initiated CSF as PP in the first cycle of chemotherapy. CSF use increased for all cancers, but most for BCa, (36% in 2002 to 70% in 2004); PP increased from 5% to 26%. Significant predictors (p<0.05) of PP were: BCa–local vs distant stage (OR 0.2), regional vs distant (OR 0.6), chemotherapy FN risk high vs low (OR 6.7); LCa–chemotherapy FN risk high vs low (OR 8.9), intermediate vs low (OR 6.3). FN incidence was 11%, 18% and 32% for BCa, CRCa, LCa, respectively. Significant predictors of FN were: BCa–nonwhite race (OR 2.7); LCa–surgery within 30 days (OR 1.7); CRCa–regional vs. distant (OR 0.4) and chemotherapy FN risk intermediate vs. low (OR 4.2). Conclusions: CSF use has increased significantly, but often in settings where efficacy is uncertain. Cancer type, stage and chemotherapy risk of FN influenced use of primary prophylaxis. Non-chemotherapy factors also appear to influence risk for FN.

No significant financial relationships to disclose.
Patterns of initial treatment and survival among older patients with glioblastoma multiforme: Evidence from SEER-Medicare data
Authors: McGarry L. J. , Morissette N. , Earle C. C. , Thompson D. , Liepa A. M.
Published: March 2020

6625

Background: There is a lack of published data describing routine treatment patterns for glioblastoma multiforme (GBM), particularly in older patients (pts). We report on initial therapies used for treatment of newly diagnosed GBM and related survival among US pts aged 65 years and older. Methods: GBM pts (ICD-O histology codes 9440–9442) were identified in the SEER-Medicare database from 1992 to 2002 and followed through 2004 or until death. Included in the analysis were pts aged 65+ years at diagnosis with no prior cancer diagnosis, enrolled in Medicare Parts A and B, and not enrolled in a Medicare health maintenance organization (HMO). Initial treatment was defined as treatment received within 1 month prior to or 3 months after diagnosis. Use of first-line treatment for GBM was analyzed over all pts, as well as by year of GBM diagnosis; Kaplan-Meier methods were used to assess survival by initial treatment. Results: 3,407 pts met all eligibility criteria. Median age at GBM diagnosis was 75 years; 51.3% of pts were male and 91.9% were white. 88.4% of pts aged 65–74 received active treatment (craniotomy, chemotherapy and/or radiotherapy [RT]), compared to 76.7% of pts aged 75–84, and 50.4% of pts aged 85+. Craniotomy plus RT was the most common initial treatment (40.4% of all pts), followed by craniotomy only (14.9%), RT only (14.7%) and craniotomy plus RT plus chemotherapy (7.8%). Complexity of treatment tended to decrease with age: multiple treatment modalities were used in 62.1% of pts aged 65–74, 42.7% of pts aged 75–84 and 21.3% of pts aged 85+. No notable trend in distribution of initial treatments was observed over the 10-year study period. Pts undergoing craniotomy plus RT plus chemotherapy survived longest (median: 7.6 months; 95% confidence interval: 7.2–8.3 months), followed by those undergoing craniotomy plus RT (6.5; 6.2–7.1). Pts undergoing craniotomy only (2.1 months; 2.0–2.2) and receiving no treatment (2.0; 1.5–2.1) had the shortest survival. Conclusions: The majority of pts aged 65 years or older receive active treatment for newly diagnosed GBM. Among these pts, receipt and complexity of treatment is highest for younger pts and tends to decrease with age. More aggressive initial therapy is associated with longer survival.

No significant financial relationships to disclose.
Clinical trial eligibility determination using an oncology electronic medical record system interfaced to a caBIG-certified trial database
Authors: Goldwein J. W. , Van Der Pas M. , Tis L. , Nickens R. , Comis R.
Published: March 2020

6626

Background: One reason for the low numbers of patients entered on cancer clinical trials is the difficulty and inconvenience encountered in determining whether patients are eligible. The introduction of electronic medical record (EMR) systems in cancer facilities provides a means by which clinical parameters may be electronically collected and compared against clinical trial eligibility criteria, with the potential to facilitate eligibility determination. We hereby describe a widely utilized EMR system interfaced to a caBIG-certified searchable clinical trials database which facilitates eligibility determination. Materials and Methods: MOSAIQ is a widely utilized oncology- specific EMR system that is operational in radiation and medical oncology facilities world-wide. During the routine course of patient care, clinical trial eligibility parameters such as diagnosis, stage, age, and performance status are entered into defined data fields within the EMR. Trialcheck is an independently maintained caBIG bronze level certified database that lists thousands of clinical trials from Cooperative Groups, NCI/PDQ, the pharmaceutical industry and trials being conducted exclusively at particular oncology facilities. TrialCheck registrants can screen trials for patient eligibility as well as filter and track the status of trials that have been activated at their facility. In addition, a real-time, secure Internet interface between MOSAIQ and TrialCheck extracts eligibility parameters from a patient record, sends that information to TrialCheck, and returns a listing of matched clinical trials. Results: In a test screen of 4 MOSAIQ EMR patients against 257 TrialCheck clinical trials, the system matched a patient with Stage IV breast cancer to 7 available trials in less 2 seconds, a patient with Stage IIIB colon cancer to 3 trials in 5 seconds, a Stage IV prostate cancer to 5 trials in 4.4 seconds, and a patient with stage II esophageal cancer to 2 trials in 3.7 seconds. Conclusion: This product demonstrates a novel and innovative solution to one of the problems inherent in the clinical trial registration process in an efficient, reliable and secure manner.

No significant financial relationships to disclose.
Extent and nature of advertising in leading hematology-oncology journals
Authors: Sieber D. , Lee J. A. , Keller J. K. , Mathiason M. A. , Go R. S.
Published: March 2020

6634

Background: Advertising in most medical journals is dominated by pharmaceuticals in part due to journal policy. This is primarily a fiscal consideration. Because advertising clearly influence physicians’ prescribing pattern, an indirect conflict of interest exists and may potentially affect patient care. The objectives of this study were to evaluate the extent of advertising in leading hematology-oncology (HO) journals published in the U.S. and to compare the findings to those of multi-specialty journals. Methods: We evaluated the following high impact journals that publish original research and included all issues issued in 2006: Journal of National Cancer Institute (JNCI), Journal of Clinical Oncology (JCO), Blood, New England Journal of Medicine (NEJM), Journal of the American Medical Association (JAMA), and Annals of Internal Medicine (AIM). Of these, only JNCI (currently not affiliated with U.S. NCI) is not owned by a medical society. The number and nature of advertising for each journal were collected. Results: There was an average of 84, 283, and 459 pages for each issue of JNCI, JCO, and Blood, respectively. Overall, HO journals allocated 20% (range, 8–32) of their pages for advertising. JCO had the most, while JNCI the least, advertising, both classified (6% vs 1% vs 1%; P = 0.001) and non-classified (26% vs 10% vs 7%; P = 0.001). Among non- classified advertising, the major categories were drugs (48.5%), journal information (14.1%), conference announcements (10.1%), research/clinical trial (7%), disease information (6.4%), continuing medical education (3.6%), and others (10.3%). Among journals, JCO had the most drug advertising (72.5%), followed by Blood (65.6%), while JNCI did not have any (0%). Compared to multi-specialty journals, HO journals had less amount of classified (3% [range, 1–6] vs 15% [range, 10–19]; P = 0.001) and non-classified (17% [range, 7–26] vs 21% [range, 18–25]; P = 0.001) advertising. Conclusions: While less than their multi-specialty counterparts, HO journals allocated a substantial proportion of their pages to advertising, the overwhelming majority of which were sponsored by pharmaceutical companies. The extent of advertising varied by journal, but was most prominent with JCO. Notably, JNCI did not have any drug advertising.

No significant financial relationships to disclose.
Hematopoietic cell transplantation (HCT) after low-dose, total body irradiation-based regimen increased leukemia-free survival (LFS) in elderly patients with cytogenetic high-risk AML compared to chemotherapy (OSHO 97 study)
Authors: Niederwieser D. , Becker C. , Krahl R. , Al-Ali H. , Lange T. , Gerhardt A. , Schulze A. , Hähling D. , Schulze M. , Freund M.
Published: March 2020

7003

Background: Even after reaching initial CR, most AML patients > 60 years relapse within 2 years of diagnosis. Cytogenetic high risk AML (abn 3q26, abn 11q23, -5/5q-, -7/7q- and complex) has an even worse prognosis. Attempts to improve survival by intensifying consolidation chemotherapy have so far failed. We investigated the role of allogeneic HCT in comparison to chemotherapy among patients with high risk cytogenetics entered into the OSHO AML 97 protocol. Methods: Initial treatment consisted of a course of induction therapy (AraC 2 g/m2 iv on day 1,3,5,7 + mitoxantrone 10 mg/m2 iv day 1 –3, repeated once in case of PR) followed by one consolidation course (AraC 240 mg/m2 iv day 1 –5 + mitoxantrone 10 mg/m2 iv day 1 –2). Patients in CR1 after the consolidation I were either treated with an additional consolidation therapy or with an allogeneic HCT from related (n=2) or unrelated (n=10) donors. Transplant patients were conditioned with fludarabine and TBI 200 cGy and immunosuppressed with cyclosporine and mycofenolate mofetil. Results: A total of 347 patients are evaluable. Of 105 (33%) patients with high-risk cytogenetics, 53 (50%) went into remission after one or two cycles of induction chemotherapy. Of these 53 patients, 42 received consolidation I and 35 patients were available for either consolidation II (n=23) or HCT (n=12). Median age of the patients receiving chemotherapy was 64 (range 61–77) years and that of the transplant patients was 64 (range 61–68) years. LFS at 4 years was 42 ± 14% after HCT and 15 ± 8% after chemotherapy. Major differences in relapse incidences were seen between the two groups, with the lowest RI at 4 years after HCT (36 ± 15%) followed by chemotherapy (85±8%, p<0.04). Treatment related mortality at 4 years was 35±17% and 0±0% for patients receiving HCT and chemotherapy, respectively (p<0.05). Conclusions: From these results, we conclude that consolidation with allogeneic HCT after minimal conditioning is superior to chemotherapy even in older patients with high risk cytogenetics. While differences in TRM were seen between the treatment arms, a lower relapse incidence after related and unrelated HCT contributed to the improved LFS.

No significant financial relationships to disclose.
A phase III randomized trial of intensive induction and consolidation chemotherapy ± oblimersen, a pro-apoptotic Bcl-2 antisense oligonucleotide in untreated acute myeloid leukemia patients >60 years old
Authors: Marcucci G. , Moser B. , Blum W. , Stock W. , Wetzler M. , Kolitz J. E. , Thakuri M. , Carter T. , Stuart R. K. , Larson R. A.
Published: March 2020

7012

Background: Overexpression of Bcl-2, an inhibitor of apoptosis, may render AML cells resistant to chemotherapy and has been associated with unfavorable outcome. Genasense is a phosphorothioate 18-mer antisense oligonucleotide directed against the first 6 codons of Bcl-2. In a phase I study of older (≥60 yrs) AML patients (pts) treated with Genasense in combination with cytarabine (Ara-C) and daunorubicin (DNR) induction and with high-dose cytarabine (HiDAC) consolidation, no antisense-related toxicity was reported. Furthermore, overexpression of Bcl-2 at diagnosis and down-regulation of the Bcl-2 target after antisense treatment was shown in pts achieving complete remission (CR). Methods: A phase III trial (CALGB 10201) randomized untreated older AML pts to induction treatment with Ara-C (100 mg/m2/d by CIVI on days 4–10) and DNR (60 mg/m2/d on days 4–6) followed by consolidation therapy with HiDAC (2 g/m2/d on days 4–8) with (Arm A) or without (Arm B) Genasense (7 mg/m2/d CIVI on days 1–10 for induction and days 1–8 for consolidation). The study was powered to identify a survival advantage for pts receiving Genasense. Results: 503 pts enrolled between 12/03 and 10/06; 76 had prior MDS and 24 prior chemoradiotherapy for unrelated cancers. The arms were balanced for age, sex, race, and performance status. No differences in toxicities were observed between the 2 arms. An interim futility analysis performed at 34 months from initiation of the study showed no differences in CR rates (48% vs 52%; p=0.75) or overall survival (OS; p=0.83) between the 2 arms. Estimated OS at 1 yr was 36% for Arm A and 40% for Arm B. Similarly, there were no differences in disease-free survival from date of CR (DFS; p=0.78) or event-free survival (EFS; p=0.77). DFS and EFS rates at 1 yr were 40% and 25% for Arm A, and 43% and 7% for Arm B, respectively. Conclusions: Addition of Genasense to induction and consolidation chemotherapy failed to improve the outcome of older AML pts. Pretreatment levels and post-antisense treatment changes in Bcl-2 expression are now being measured and correlated with outcome.

No significant financial relationships to disclose.
Trough plasma imatinib concentrations are associated with responses to standard-dose imatinib in chronic myeloid leukemia and could improve its clinical management
Authors: Mahon F. , Etienne G. , Picard S. , Titier K. , Marit G. , Begaud B. , Reiffers J. , Moore N. , Molimard M.
Published: March 2020

7027

Background: Variable responses to imatinib in the treatment of myelogenous leukemia (CML) are incompletely understood. Previous studies focused on cellular mechanisms of resistance to imatinib. Another hypothesis for variable response lies in pharmacokinetic variability that may reduce drug exposure in patients receiving imatinib. Methods: Using high- performance liquid chromatography-tandem mass spectrometry, we assessed trough plasma imatinib concentrations at steady state (Cmin) in more than 150 CML patients. Major molecular response (MMR) was defined as a 3 logarithm reduction of BCR-ABL transcripts, quantified from peripheral blood using Q-RTPCR. In addition, suboptimal response criteria defined by the European Leukemianet were used to increase doses of imatinib. Results: i) we assessed Cmin in 85 CML patients and demonstated a correlation with imatinib doses (median values 813, 1,135, 1,709 ng/ml for respectively 300,400, 600 mg/day). ii) for 68 patients after at least one year's treatment mean Cmin were significantly higher in the group with MMR (34 patients) than in the group without (1,452.1±649.1 ng per milliliter vs. 869.3±427.5 ng per milliliter, P<0.001) whereas there was no difference in the imatinib daily dose. For Cmin and their discrimination potential for MMR, the area under receiver-operating characteristic curve was 0.775, with best sensitivity (76.5 percent) and specificity (70.6 percent) at a plasma threshold of 1,002 ng per milliliter. iii) dose escalation of imatinid, 400mg up to 600mg was proposed in 8 patients in suboptimal response (3 according to cytogenetic criteria and 5 according to molecular criteria). The median Cmin increase from 573 ng/ml [181–1,376] to 1,139 ng/ml [733–2,262] and 5 patients had a cytogenetic (n=3) or a molecular (n=2) response. Conclusions: Monitoring of imatinib plasma levels could be very useful for the management of CML patients, or should at least be checked in the case of treatment failure or suboptimal response or in patients nonadherent with imatinib or with a drug-drug interaction suspicion.

No significant financial relationships to disclose.
Beta-2 microglobulin (B2M) is an independent prognostic factor for clinical outcomes in patients with CLL treated with frontline fludarabine, cyclophosphamide, and rituximab (FCR) regardless of age, creatinine clearance (CrCl)
Authors: Tsimberidou A. M. , Tam C. , Wierda W. , O' Brien S. , Lerner S. , Keating M. J.
Published: March 2020

7034

Introduction: High β2M levels are a risk factor in CLL. PCR therapy has been reported to be better tolerated than FCR in older or with decrease renal function pts (Shanafelt, Blood 108:15a). We assessed the association between age, CrCl, PS, β2M and outcomes in pts treated with FCR. Methods: From 7/99 to 1/04, 300 pts received rituximab 375 mg/m2 D1; fludarabine 25 mg/m2/d D2–3; and cyclophosphamide 250 mg/m2/d D2–3. Serum β2M levels were measured by radioimmunoassay. CrCl was calculated (Cockcroft-Gault equation). Results: The median age was 57 yrs (≥70, 14%). Age ≥70 was associated with fewer FCR courses (p<.0001); lower rates of CR (p=.001), overall response (OR; p=.04), survival (OS; p<.0001), and FFS (p=.008); and higher rates of G3–4 thrombopenia (p<.0001) or anemia (p=.002) compared with age<70. The median CrCl was 90 mL/min (CrCl <70, 27%). Pts with CrCl <70 had higher rates of G3–4 thrombopenia (p=.006) or anemia (p=.01) than others. There were no differences between the 2 groups in the other outcomes. PS was 0 in 40%, 1 in 57%, and 2 in 3% of pts. Better PS was associated with higher rates of CR (p=.007) and FFS (p=.02) but did not affect OR or OS. The median β2M level was 3.7 mg/L (β2M ≥ 4, 43%). The rates of CR, survival, and FFS were lower in pts with β2M ≥ 4 compared with others (p<.0001 each). High β2M levels were associated with older age, lower CrCl levels, poorer PS (p<.0001 each), higher rates of G3–4 neutropenia (p=.005), thrombocytopenia (p=.01), and infections (p=.03), and fewer FCR courses (p=.004). The median follow-up was 5 yrs. The rates of CR, 3-yr OS and 3-yr FFS were 72%, 87% and 76%, respectively. Independent factors predicting response were lower β2M (p=.0004) and lower WBC counts (p=.02). Independent factors predicting longer OS were younger age (p=.001), lower β2M (p=.003) and lower WBC (p=.03). Independent factors predicting longer FFS were lower β2M levels (p=.0006), and lower WBC counts (p=.005). Conclusion: Age ≥70 yrs and poor PS, but not CrCl level were associated with poor clinical outcomes. High β2M levels are an independent adverse prognostic factor for CR, OS, and FFS in the context of other prognostic factors.

No significant financial relationships to disclose.
Five-year follow-up results of imatinib 400 mg in late chronic phase chronic myeloid leukemia (CML) patients
Authors: Iacobucci I. , Palandri F. , Amabile M. , Poerio A. , Soverini S. , Castagnetti F. , Testoni N. , Rosti G. , Baccarani M. , Martinelli G. , Palandri F.
Published: March 2020

7041

Background: Imatinib (IM) is the drug of choice for the treatment of Ph+ CML, where a complete cytogenetic response (CCgR) is achieved in more than 80% of early chronic phase (ECP) patients, with a 6-year survival of 89%. Methods: We monitored the hematologic, cytogenetic and molecular response to imatinib in a cohort of 295 patients with Ph+ CML in late chronic phase (LCP) who were enrolled in a national prospective study of the GIMEMA CML Working Party, with focus on the rate of major molecular response and on progression-free survival and overall survival of complete cytogenetic responders. Patients were monitored for cytogenetic and molecular response every 6 months. Cytogenetics was performed on bone marrow cells with conventional methods. Molecular response was assessed on peripheral blood samples by quantitative PCR (RQ-PCR) using TaqMan methodology and expressing the results as a ratio of BCR-ABL to ABL x100. The duration of chronic phase prior to IM treatment ranged from 1 to 202 months (median 38). Treatment was IM 400 mg daily through all the study period, with a few dose increase to 600 or 800 mg. Results: 158 patients (54%) achieved a CCgR in 3 to 62 months (median 6) after the first IM dose and 124 of them (78%) are still in continuous CCgR after 5 years whereas 34 patients lost the CCgR, 23 of them within 24 months after the CCgR achievement. For the 158 patients the 5-year survival free from progression to accelerated or blastic phase is 95% and overall survival is 91%. 114 patients were evaluable for molecular response and 68% of them were in major molecular response with a BCR-ABL/ABL ratio lower than 0.05. Conclusions: We showed that for the complete cytogenetic responders progression-free and overall survival are likely to be as good as for ECP patients, suggesting that the quality of the cytogenetic response is prognostically more important than the chronic phase duration before IM start. Supported by European LeukemiaNet, COFIN 2003, AIL, AIRC.

No significant financial relationships to disclose.