bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding patient expectations in early-phase clinical trials
Authors: Weinfurt K. P. , Seils D. M. , Tzeng J. P. , Compton K. L. , Sulmasy D. P. , Astrow A. B. , Schulman K. A. , Meropol N. J.
Published: March 2020

6543

Background: Participants in early-phase clinical trials have reported high expectations of benefit from their participation. There is concern that participants misunderstand the trials to which they have consented. Such concerns are based on assumptions about what patients mean when they respond to questions about likelihood of benefit. In this study, we explored some of these assumptions. Methods: Participants were 27 women and 18 men in phase 1 or 2 oncology trials and randomized to 1 of 3 interview protocols corresponding to 3 target questions about likelihood of benefit: frequency-type (‘Out of 100 patients who participate in this study, how many do you expect will have their cancer controlled as a result of the experimental therapy?‘); belief-type (‘How confident are you that the experimental therapy will control your cancer?‘); and vague (‘What is the chance that the experimental therapy will control cancer?‘). In semistructured interviews, we queried participants about how they understood and answered the target question. Each participant then answered and discussed one of the other target questions. Results: Participants tended to provide higher expectations in response to the belief-type question (median, 80) than in response to the frequency-type or vague questions (medians, 50) (P=.02). Only 7 (16%) participants said their answers were based on what they were told during the consent process. The most common justifications for responses involved positive attitude (n=27 [60%]) and references to physical health (n=23 [51%]). References to positive attitude were most common among participants with high (>70%) expectations of benefit (n=11 [85%]) and least common among those with low (<50%) expectations of benefit (n=3 [27%]) (P=.04). Conclusions: We identified two factors that should be considered when determining whether high expectations of benefit are signs of misunderstanding. First, participants report different expectations of benefit depending on how the question is asked. Second, the justifications participants give for their answers suggest that many participants use their responses to express hope rather than to describe their understanding of the clinical trial. These findings should inform methods for evaluating the quality of informed consent in early-phase trials.

No significant financial relationships to disclose.
Beware of the isolated intermediate quality measure: A lesson in choosing an ovarian cancer surgeon
Authors: Silber J. H. , Rosenbaum P. R. , Polsky D. , Millman A. M. , Ross R. N. , Even-Shoshan O. , Schwartz J. S. , Armstrong K. , Randall T.
Published: March 2020

6546

Background: Measuring surgical quality has recently focused on isolated processes (such as P4P measures) and intermediate outcomes (such as infection rates). Some have argued that such isolated measures are inherently flawed since they may have only minor influence on more important primary outcomes such as survival. Hence, referral decisions based on such isolated processes or intermediate outcomes may lead to less than optimal care. We asked whether surgeon type influenced isolated process measures (longer operative time, thought to be a function of increased node sampling), intermediate outcomes (deep wound infection, often found to be a function of operative time) and the primary outcome of survival. Methods: We obtained SEER-Medicare claims for the years 1991–2001 for ovarian cancer. We identified the first definitive cancer surgery and the surgical provider type for that procedure: General Surgeon (GS) N=545 and GYN Oncologist (GO) N=1,554. We determined operative time from the anesthesia claims, number of nodes sampled from the SEER record, deep wound infection from the ICD9CM secondary diagnoses and survival from Medicare vital status files. Models were adjusted for 30 patient characteristics and comorbidities. To account for potential reclassification bias due to variations in the pattern of node dissection across GO and GS surgical types, which can potentially influence stage identification, we report survival results both with and without stage adjustments. Results: Definitive surgery by GOs was associated with more extensive node dissection and longer operative time. GO patients also displayed a trend for increased deep wound infection as compared to cases operated on by GS. However, 5-year survival was significantly longer in the GO group, with or without stage adjustment. Conclusions: GO cases took longer, tended to have higher infection rates, yet had better overall 5-year survival. Isolated intermediate outcome measures, such as deep wound infection, may not be good quality indicators.

No significant financial relationships to disclose.

[Table: see text]
Factors associated with reductions in chemotherapy dose intensity: Impact of clinical, sociodemographic and practice setting
Authors: Lyman G. H. , Kuderer N. M. , Poniewierski M. S. , Crawford J. , Wolff D. A. , Culakova E. , Dale D. C.
Published: March 2020

6550

Background: A nationwide, prospective cohort study of patients receiving cancer chemotherapy was undertaken to better define treatment-associated toxicities and delivered dose intensity. Methods: Following informed consent, 3,670 patients initiating a new chemotherapy regimen with lymphoma (n=547) or carcinomas of the colon (n=521), breast (n=1,473), lung (n=907) or ovary (n=312) were prospectively registered at 117 randomly selected US oncology practices between March 2002 and December 2005. Pretreatment characteristics including clinical and sociodemographic factors and practice setting associated with reductions in chemotherapy dose intensity over 4 cycles were evaluated. Results: Chemotherapy regimen standards and intended dose and schedule were defined in 97% and 93% of patients, respectively. Average initial (planned) relative dose intensity (RDI) was 90% while the mean RDI actually delivered over 4 cycles was 83%. Reductions in RDI =15% of standard were planned in 23% of patients and actually occurred over 4 cycles in 38%. Body surface area (BSA) calculated by the method of Mosteller exceeded the BSA utilized by the oncology practices in two-thirds of patients most often due to capping at 2 m2. Obese patients with a body mass index (BMI) =30 were more likely to receive planned RDI reductions =15% (30%) than patients with BMI <30 (21%) (P<.0001). Other factors associated with planned reductions in RDI in multivariate analysis included: older age, male gender, lower education, absence of myeloid growth factor prophylaxis and cancers of the lung or ovary as well as the practice setting, size and geographic location. Factors associated with unplanned (subsequent) reductions in RDI included: older age, male gender, poorer Charlson comorbidity index, prior chemotherapy, lung cancer, low baseline hematocrit, white blood or platelet count, poor renal or hepatic function and low serum albumin as well as smaller practice and rural setting. Conclusions: A substantial proportion of patients receiving cancer chemotherapy experience both planned and unplanned reductions in RDI. Further understanding of factors associated with such reductions may provide opportunities for improving the quality of cancer care and clinical outcomes.

No significant financial relationships to disclose.
Comorbidity, age and stage at diagnosis in colorectal cancer (CRC)
Authors: Zafar Y. , Abernethy A. P. , Abbott D. H. , Herndon J. E. , Rowe K. , Kolimaga J. , Conner L. , Patwardhan M. , Grambow S. , Provenzale D.
Published: March 2020

6554

Background: Stage at diagnosis is a crucial predictor of outcome in CRC. The purpose of this study is to determine if comorbidity and age affect the stage at which CRC is diagnosed. Identifying variables that influence stage might improve outcomes in CRC. Due to frequent contact with the health care system, we hypothesize that patients with greater comorbidity and older age are more likely to be diagnosed with early-stage disease. Methods: We present data from two distinct patient populations: using the Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) database, we identified CRC patients treated at 15 Veterans Administration (VA) hospitals from 2003-present. We also identified CRC patients treated from 2003-present at 10 non-VA, fee-for-service (FFS) practices in North and South Carolina. Data were abstracted by retrospective chart review. Comorbidity was calculated by the Charlson comorbidity index (CCI) with high comorbidity defined as CCI =3. Older age was defined as age =70 years. Data were analyzed using logistic regression where the odds of late stage at diagnosis were modeled as influenced by older age, high CCI, and race. The analysis included estimation of adjusted and unadjusted odds ratios. Results: 347 VA and 282 FFS patients were included. 98% VA vs 50% FFS were male; 43% VA vs 27% FFS were aged =70; 56% VA vs 70% FFS were white; 26% VA vs 44% FFS presented with metastatic CRC; and 21% VA vs 6% FFS had a CCI =3. In both patient populations, regression analysis showed that older age, high CCI and white race were not significant predictors of stage at diagnosis. VA 95% confidence intervals (CI's) were 0.52–1.41 (age =70), 0.50–1.75 (CCI =3), and 0.42–1.11 (white race). FFS 95% CI's were 0.52–1.53 (age =70), 0.36–2.78 (CCI =3), and 0.74–2.11 (white race). Broader 95% CI's in the FFS analysis were due to smaller sample size. Conclusions: In CRC patients, age and comorbidity were not related to stage at diagnosis. The findings are similar whether the patients were treated in a fee-for-service or VA health system. While older age and greater illness might provide more contact with the health care system, this exposure did not result in earlier diagnosis of CRC. Future studies will examine the impact of comorbidity on CRC treatment and survival.

No significant financial relationships to disclose.
Patient-reported outcome (PRO)-assessed clinical benefit with panitumumab (Pmab) in metastatic colorectal cancer (mCRC) patients (pts)
Authors: Hendlisz A. , Van Cutsem E. , Peeters M. , Humblet Y. , Neyns B. , Sobrero A. , Devercelli G. , Wolf M. , Amado R. G. , Siena S.
Published: March 2020

6560

Background: In a phase III study of mCRC pts, Pmab monotherapy significantly improved partial response (PR) rates and progression-free survival (PFS) compared with best supportive care (BSC). This analysis characterizes the clinical benefit of PR/stable disease (SD) and PFS in mCRC pts with respect to health-related quality of life (HRQoL) and CRC symptoms. Methods: Pts had documented disease progression (DP) after treatment (tx) with fluoropyrimidine-, irinotecan-, and oxaliplatin- containing chemotherapy regimens. Pts were randomized 1:1 to receive BSC + Pmab 6mg/kg Q2W. HRQoL (EQ-5D and EORTC QLQ-C30 Global QoL subscale) and CRC symptoms (NCCN/FACT CRC symptom index, FCSI) were assessed at baseline, at least Q4W during tx, and at the 30 day safety follow-up visit. Only pts with PFS ≥ 56 days were included in the analysis to minimize potential lead-time bias associated with response evaluation. T-tests and least square estimates were calculated for differences in PRO measures at 4, 8, 12, 16, and 20 weeks controlling for baseline score by best response (PR or SD vs. other) and by tx arm. Imputation of missing data incorporated each pt's rate of change to assign missing values. Results: In the Pmab arm (n=231), 36% of pts had PR or SD; in the BSC arm (n=232) 10% of pts had SD (no PRs). 109 Pmab pts and 63 BSC pts had at least 1 post-baseline PRO assessment and a PFS time ≥ 56 days. In the Pmab arm, pts with a best response of PR or SD (n=73) had significantly higher mean HRQoL scores at all 5 time points (indicating better HRQoL) compared to those with a best response of < SD (n=36, p=0.03). Consistent results were observed between pts with a best response of PR/SD and CRC symptom scores (p=0.002), indicating less CRC symptomatology. However, in the BSC arm, pts with SD (n=20) had no significant differences in HRQoL or CRC symptoms at any time point compared to pts with < SD (n=43, p=0.12). Results were consistent across all instruments and imputation methods used. Conclusions: These findings show that among Pmab pts with PFS ≥ 56 days, those who had a best response of PR or SD experience significantly higher HRQoL and less CRC symptomatology than Pmab pts without a response. These data suggest that delaying DP may result in clinical benefit.

[Table: see text]
Screening and genetic counseling practices for hereditary non-polyposis colorectal cancer (HNPCC)
Authors: Karri S. , Govindarajan S. R. , Bendure W. B. , Jackson S. A. , McKelvey K. D. , Govindarajan R.
Published: March 2020

6564

Background: HNPCC, the most common cause of hereditary colorectal cancer (CRC), is inherited in an autosomal dominant fashion and caused by micro satellite instability and mutations in mismatch repair genes. Affected patients (pts) and first degree relatives tend to develop colonic and extra colonic tumors that need to be tested for the mutations. Genetic consultation (GC) should be routinely offered to the affected pts and relatives. To assess the utilization of GC, we assessed the frequency of referral for GC for the presence of HNPCC syndrome at our medical center. Methods: Patients with CRC were identified from the tumor registry at the University of Arkansas for Medical Sciences (UAMS) and the Central Arkansas Veterans Healthcare System (CAVHS) from January 1st 2000 to September, 2006. Pts’ charts were reviewed for synchronous or metachronous HNPCC tumors and family history (FH). FH was categorized as positive according to the Bethesda criteria (BC, 2000–2002), revised Bethesda criteria (RBC, 2003–2006), negative (documented FH but no h/o cancer) or inadequate documentation. Percentage of pts with positive FH for HNPCC syndrome and those with CRC less than 50 years of age (for pts diagnosed 2003–2006) who were referred for GC was calculated. The list of these pts was cross referenced to the list in genetics clinic at UAMS and CAVHS. Results: 858 patient charts were reviewed. Table 1 shows the number of pts meeting criteria for genetic counseling. 138 (16%) pts had inadequate /no documented FH. Of the 720 pts with documented FH, 67 (9.3%) had positive FH and 126(17%) met BC / RBC. Only 13 (10.3%) of 126 pts were referred for genetic counseling. The number of pts eligible for GC increased with inclusion of RBC. However, the percentage of eligible pts referred for GC was extremely low. Conclusions: FH is not adequately documented in many pts presenting with CRC. Only a small percentage of pts who qualify for GC are referred. Education of health care providers for referral to genetics counseling is warranted.

No significant financial relationships to disclose.

[Table: see text]
The case for proactive, collaborative data-updating in a statewide cancer clinical trial matching service
Authors: Moffitt K. , Marsh R. D. , Hudson C.
Published: March 2020

6570

Background Florida has the second highest cancer incidence of any state in the United States. To address Florida's growing cancer burden and the need for increased clinical trial participation, Florida Cancer Trials (FCT) launched a web-based and phone-based Clinical Trial Matching Service for the State of Florida on November 1, 2004 (operated by EmergingMed). After 2 years of monthly outreach to 96 trial sites, the FCT wanted to assess the outcome and ongoing need for intensive, grass-roots data verification activities in light of other publicly available cancer clinical trial databases. Methods On 10/23/06, FCT staff extracted all trials containing at least one Florida trial site from the PDQ and ClinicalTrials.gov (CT.gov) database. The same extraction was produced from the TrialCheck database on 11/10/06. Each database was compared to the list of active cancer clinical trials in the FCT/EmergingMed database on the same day. Every trial-site listed in the PDQ/CT.gov database, but missing from the FCT/EmergingMed database, was contacted by FCT staff to confirm the accuracy of each trial/site combination. Results PDQ/CT.gov contained 547 trials listed with Florida trial sites on 10/23/06 (the FCT/EmergingMed database contained 526 trials on the same day). On 11/10/06, the TrialCheck database listed 528 trials with Florida trial sites (the FCT/EmergingMed database contained 513 verified trials on the same day). The PDQ/CT.gov database was missing 25% of Florida's open trials, while the TrialCheck database was missing 36% of Florida's open trials. Moreover, 19% of PDQ/CT.gov's trial listings and 25% of TrialCheck's listings for Florida were erroneous. Conclusions With 25%–36% of Florida's trials missing from public databases, and 19%–25% of their current listings being false listings for Florida, the FCT continues to conclude that a grass-roots, monthly data verification schedule is necessary to maintain a cancer clinical trial database that is suitable for use in referring patients and physicians to Florida's cancer clinical trial sites.

No significant financial relationships to disclose.
Association of serious adverse events with type and sponsorship of clinical trials in patients with lymphoma
Authors: Koeneke T. L. , Armitage J. O. , Bierman P. J. , Bociek R. , Vose J. M. , Loberiza F. R.
Published: March 2020

6576

Background: Arguments have been made against early phase clinical trials (CTs) as possibly being unethical because its risk may outweigh its potential benefits. Whether this is true in the light of newer biological treatment for cancer is unknown. We therefore examined the association between the incidence of serious adverse events according to type and sponsorship of CTs in pts with lymphoma. Methods: All IRB approved CTs at the University of Nebraska Medical Center from Jan 2000-June 2005 classified as therapeutic for lymphoma involving a biological agent were included. CTs were classified in two ways: by type of CTs (phase I vs II vs III) and sponsorship (Investigator-initiated vs Industry-initiated. Multivariate logistic regression was used to evaluate the association between types/sponsorship of CTs with the incidence of IRB serious adverse events (SAE; no vs yes) and fatal adverse events (FAE; no vs yes) while adjusting for age, sex, race, lymphoma type and stage, interval from dx to tx, co-morbid conditions, and previous tx. Results: 357 pts with lymphoma enrolled in 29 CTs were included. The median age of pt was 54y (21–88). 41% of the pts had follicular lymphoma, 36% diffuse large cell, 14% mantle cell and 9% were other types. 59% had Stage IV lymphoma. 71% of the pts participated in investigator-initiated CTs, while 29% participated in industry-initiated CTs. 21% of pts were enrolled in phase I, 65% in phase II and 14% in phase III studies. SAEs were seen in 49 pts (14%), while FAEs occurred in 13 pts (4%). Multivariate analysis showed the risk of having SAE was independent of the type or sponsor of CTs. Additionally, the risk of FAEs was not associated with the type of CTs. However, the risk of having FAEs was less in investigator- iniatiated CTs than in industry-iniatiated trials (Odds Ratio: 0.13 (95% CI, 0.03–0.61, p = 0.01). Conclusions: Our study showed that in CTs involving biological treatments, the incidence of SAEs was not associated with the type or sponsor of CTs suggesting that use of biological agents in phase I studies may have similar risks to phase II/III trials. Further studies should be done in other types of malignancies to evaluate further the decrease frequency of FAEs seen in investigator-initiated trials.

No significant financial relationships to disclose.
Assessing community hospital compliance with NCCN breast cancer guidelines in diagnosis and treatment of stage IIb and IIIa breast cancer: A Fox Chase Cancer Center Partners (FCCCP) initiative
Authors: Gitelson E. , O'Grady M. , Swaby R. F. , Goldstein L. J. , Li T. , Engstrom P. F. , Cohen S. J.
Published: March 2020

6578

Background: The majority of cancer treatment occurs in community settings. NCCN guidelines are widely regarded as a marker for quality cancer care. We performed a retrospective review to assess compliance with NCCN guidelines at community medical oncology practices affiliated with FCCCP. Methods: Outpatient charts of 277 patients diagnosed with stage IIb/IIIa breast cancer between 2002–2005 from 16 medical oncology practices were assessed for the following documentation: charted pathology report with stage, ER, PR, and HER2/neu status noted, menopausal status, diagnostic mammogram, surgical evaluation, and radiation oncology consultation. The following treatments were evaluated: irradiation post-lumpectomy, sentinel and/or full axillary lymph node dissection (SLND and/or ALND), number of lymph nodes resected if ALND, use and type of chemotherapy, and accrual to a clinical trial. Results were compared with corresponding NCCN guidelines. Results: Percent compliance with NCCN guidelines by parameter for documentation were: pathology report (90.2%), staging (100%), ER/PR (92.4%), HER2/neu status (87.5%), menopausal status (92.3%), results of diagnostic mammogram (83.2%), and consultations of surgical (92.8%) and radiation oncologists (76%). For treatment, 85.1% of women had radiation post lumpectomy. SLND and/or ALND were performed in 96% of surgeries, with full ALND performed in 99% of cases with positive SLN. Eight or more lymph nodes were evaluated in 71.9% of patients. Overall, 83.7% of patients underwent chemotherapy, with 78.7% receiving regimens in compliance with NCCN guidelines. Clinical trial accrual was 6.2%, exceeding American College of Surgeons commendation standards for comprehensive community programs. Overall, mean percent compliance per NCCN parameter among practice groups was 87.8% (range 41.6 - 96%), with 15/16 hospitals achieving mean compliance above 80%. Conclusions: A comprehensive quality benchmark assessment of community medical oncology offices using NCCN guidelines is feasible. While overall compliance is high, areas deserving of education and improvement can be identified.

No significant financial relationships to disclose.
Coaching intervention as a strategy for enhancing accrual to phase I/II clinical trials
Authors: Fracasso P. M. , Walker M. S. , Mathews K. J. , Morgan H. P. , Goodner S. A. , Foster D. M. , Hardmon A. A. , Creekmore A. N. , Springer B. C. , Fisher E. B.
Published: March 2020

6580

Background: Lack of both trust and rapport with health care providers has been identified as possible causes for under- representation of minorities within clinical trials. Our study used a “Peer Coach” (PC) to promote trust among minority patients with advanced cancer. Methods: Minority patients with advanced breast, colorectal, lung, or prostate carcinoma were randomly assigned to receive a PC or “Usual Care” (UC). Patients completed baseline and 6-month telephone interviews to assess demographics, trust in healthcare providers, attitudes toward clinical trials, and quality of life. Patients randomized to the coaching intervention were assigned a coach, trained in health communications, who made biweekly contacts for 6 months to address general issues, progress or development in cancer care, and available resources. Patients randomized to UC received no further intervention. Results: Over 21 months, we screened 268 patients and enrolled 73 African Americans and 2 Asians (56 women and 19 men) including 38, 18, 13, and 6 patients with breast, colorectal, lung and prostate cancers, respectively. Patients were randomly assigned to PC (38) and UC (37), with no baseline differences. Longitudinal data analysis was conducted on 69 patients who completed the 6-month follow-up assessment. Trial enrollment was slightly higher in the PC group but was found to be non-significant (p=0.226). Trust in doctor (p=0.053), absence of depressed mood (p=0.032) and higher quality of life (p=0.052) predicted enrollment. Adherence to care was unrelated to the assigned group and, in the PC group, to the number of coach contacts. Baseline depression was associated with missed physician appointments (p=0.039). There was no difference between the PC and UC groups on attitudes towards clinical trials, perceptions of racism, trust in doctor, medical mistrust, depression, or quality of life. Conclusions: Psychosocial elements of trust in doctor, depression and quality of life were found to predict trial enrollment, regardless of assignment to PC or UC. Future studies should include a more structured approach to clinical trial promotion, follow patients over a longer period, and consider treatment of depression given its association with trial enrollment and adherence.

No significant financial relationships to disclose.
The usefulness of the intensity of 18fluorodeoxyglucose uptake in positron emission tomography (FDG-PET) in distinguishing between indolent and aggressive non-Hodgkin's lymphomas
Authors: Sobrevilla-Calvo P. , Chalapud J. , Rivas -Vera S. , Altamirano-Ley J.
Published: March 2020

6584

Purpose: FDG PET is recommended for the initial evaluation and staging of patients with non-Hodgkin's lymphoma (NHL). We investigated whether the intensity of tumor FDG uptake in NHL is significantly different between indolent and aggressive histology. Materials and Methods: We studied a retrospective cohort of lymphoma patients with NHL, attended at a single tertiary care center from April 2003 to November 2006 and who had not received treatment. We reviewed the initial, re-staging and/or relapse PET studies of 50 patients with diagnosis of NHL. Mean age 42 (15 to 72) years, 27 female and 23 male. We recorded the highest standardized uptake value (SUV), correlations were made with histopathology. We analyzed SUVs considering the various histologies and grades. Two sample comparisons were performed using the Wilcoxon test. Results: The histopathological diagnoses were: diffuse large B-cell lymphomas (26 patients), anaplastic large cell lymphoma (7 patients), Follicular lymphoma (14 patients), and other types (3 patients, 1 MALT, 1 Burkitt and 1 small cell Burkitt-like). FDG uptake was lower in indolent (15 patients) than aggressive lymphoma (35 patients) (SUV, mean 6.2, SD Â ± 1.7, mean rank 15.47, sum of ranks 232 vs 12.9 Â ± 7.4, mean rank 29.8, sum of ranks 1,043; P=.001). Despite overlap between indolent and aggressive disease in the low SUV range (indolent 3.7 to 9.3; aggressive 3.2 to 24.9) all cases of indolent lymphoma had an SUV â‰¤ 9.3. Conclusion: FDG uptake is significantly lower in indolent than in aggressive lymphoma. Patients with NHL and SUV > 10 have a high likelihood for aggressive disease. As with other retrospective studies, this information should be confirmed prospectively, but this data allows formulating new hypothesis about correlations between the SUV, the molecular subtypes and the clinical behaviour of the lymphomas

No significant financial relationships to disclose.
Killing time: Treatment delay and breast cancer survival
Authors: Sheinfeld Gorin S. , Heck J. E. , Cheng B.
Published: March 2020

6589

Introduction: Treatment delay is commonly associated with reduced breast cancer survival. Inadequate or delayed follow-up for positive findings is the most common reason for breast cancer-related litigation in the U.S. The United Kingdom has made improvements in the delivery of breast cancer services a priority for resources with the aim of reducing delays. Yet, the evidence for the association of delay and breast cancer survival is mixed. Most studies rely on small, non-representative cohorts, treatment approaches have changed over the time since the the most widely-cited review. Studies cite wide variations in delay, and some research is subject to publication or lead time bias. Aims. The purpose of this study is to examine the influence of 3-month breast cancer treatment delay on survival using a large, longitudinal, population-based dataset to provide more definitive findings. Methods: Subjects were 43,359 female Medicare enrollees age 65 and older who were diagnosed with breast cancer between 1992 and 1999 and identified by the Surveillance, Epidemiology, and End Results (SEER) program for whom treatment delay information could be obtained. Billing claims from inpatient, outpatient and provider visits were used. Mortality from breast cancer was assessed through SEER linkage with death certificates. Using propensity scores to balance the comparison groups, the association between treatment delays of three months or more and cancer survival time were analyzed using Cox proportional hazards models with gamma frailty to account for the clustering effect due to census tract. To account for known predictors of breast cancer survival, in addition to the propensity scores, we adjusted for cancer stage, comorbidity, marital status, tumor characteristics, location, detection by screening or diagnostic mammography, and the average number of health provider visits during the study period. Results: Subjects who had over a three month delay in receiving any treatment had a 34% increased risk of breast cancer death by comparison to women with delays less than three months (adjusted Hazard ratio 1.34, 1.01–1.77). Discussion: Three-month delays in accessing breast cancer treatment have a clear relationship to survival. Rapid access to treatment is recommended for all women with breast cancer.

No significant financial relationships to disclose.
Objective response evaluations using RECIST criteria: Performance of duplicate readings
Authors: Zaim S. , Ounadjela S. , Bouzegaou N. , Szechinski J. , Appel R. , Jacques Z. , Jacques Z. , Guermazi A.
Published: March 2020

6602

Background: Duplicate readings using the RECIST criteria are the current practice for objective response evaluation in cancer trials. In this study we evaluated the agreement in the duplicate readings and the reasons of discrepancies. Methods: 179 subjects participating in a prospective trial with advanced or metastatic renal cell carcinoma were included. Imaging data consisted of chest, abdomen and pelvis CT scans. Additional imaging studies included brain CT scans at baseline and any additional images there were performed at follow up visits. The median number of total visits collected was seven. Duplicate independent evaluations using the RECIST criteria were performed by two trained onco-radiologists. The evaluations included the identification and measurement of target lesions and non- target lesions as well as new lesions. For each visit an overall response was assigned. At the conclusion of the evaluations a best response and the date of the best response were recorded. Criteria of agreement between the two radiologists were based on the best response, the date of best response and the date of progression. Results: There was perfect agreement in 145 (81.1%) of the patients. For 34 (18.9%) there was disagreement in the best response: n=14 (7.8%), in the date of best response: n=7 (3.9%) and the date of progression: n=28 (15.6%). Of the 34 patients, disagreement was on one criterion in 24 (13.4%), 2 criteria for 7 (3.9%) and all three criteria for 3 (1.6%). Conclusions: For objective response evaluations using the RECIST criteria, using the best response and time to progression as criteria for comparison of duplicate independent radiologist evaluations yields to a very good level of agreement.

[Table: see text]
Comparison of four strategies of follow-up in thyroid cancer patients: A cost-utility analysis
Authors: de Pouvourville G. , Borget I. , Allyn M. , Schlumberger M.
Published: March 2020

6606

Background: In thyroid cancer patients, follow-up is designed to detect recurrent disease and consists of neck- ultrasonography (US), thyroglobulin measurement (Tg) and radioiodine whole body scan (WBS). Recent guidelines have restricted the use of WBS to suspicious cases. To insure diagnostic accuracy, follow-up control requires TSH stimulation, either with thyroid hormone withdrawal (THW) or rhTSH, which have demonstrated similar diagnostic accuracy. THW induces significant morbidity associated with hypothyroidism, leading to a decrease in patient quality of life and ability to work, whereas rhTSH is an innovative costly drug that avoids such patient burden. A societal cost-utility analysis was conducted to compare 4 follow-up strategies, combining a method of stimulation (rhTSH or THW) and a testing protocol (US+Tg+WBS or US+Tg alone). Methods: A Markov model was built to describe the follow-up of thyroid cancer patients first treated by thyroidectomy and radioiodine ablation, over 5 years. Estimates for diagnostic accuracy values and recurrence rate were extracted from a French multicenter randomized trial. Costs were computed from the perspective of the society, including medical resources consumed (hospitalisation, rhTSH, tests, treatment of recurrence). The model also incorporated the benefits of rhTSH in terms of quality of life (utility scores derived from SF36) and the reduction in duration and overall cost of sick leave. Results: Among the 753 patients included, 13 patients presented recurrence. rhTSH stimulation resulted in a higher utility score (0.802 vs. 0.637) over the period of stimulation and a reduction of 1083 € of absenteeism costs in active patients. As compared to the THW+Tg+US+WBS strategy, the incremental cost-utility ratios (ICER) showed economic dominance for the rhTSH strategies with ratios of −16,876 and −19,297 €/QALY with and without WBS respectively. The ICER for the strategy THW+US+Tg reached 29,333 €/QALY, as compared to THW+Tg+US+WBS strategy. Conclusions: the recommended strategy combining Tg determination and US after rhTSH stimulation appears the most cost-effective in the follow-up of thyroid cancer patients, as it is the strategy the less costly and associated with improved patient quality of life.

No significant financial relationships to disclose.
Early termination of adjuvant therapy for breast and colorectal cancers
Authors: Lipscomb J. , Gillespie T. W. , Ward K. C. , Goodman M.
Published: March 2020

6610

Background. Recent patterns-of-care studies report that cancer patients often do not complete prescribed therapy, with potentially important implications for clinical outcomes including survival. Yet, little is known about the frequency and determinants of early treatment discontinuation. The aims of this study were to address these issues in a largely rural population of a 33-county region of southwest Georgia. Methods. A total of 3,996 cases of breast, colorectal (CRC), lung, and prostate cancer diagnosed between 2001 and 2003 were identified from the Georgia Comprehensive Cancer Registry, with data collected from medical records by trained abstractors; 3,949 cases were available for analysis. Since completion of adjuvant chemotherapy with a goal of cure may be particularly important, this report focuses on cases treated for stage I and II breast cancer and stage III CRC. Results. Among 854 stage I-II breast cancer cases, 323 (38%) received chemotherapy. In 293 of those cases, treatment was stopped within the first year post-diagnosis. The primary reasons for stopping included treatment completion (86%), significant toxicity (8%), or other clinical reasons (2%). In only seven cases (2%) was treatment discontinued due to patient factors (e.g. refusal or did not return to clinic). Among 179 stage III CRC cases, 124 (69%) received adjuvant chemotherapy; in 117 cases chemotherapy was stopped within 12 months following diagnosis. Clinical reasons for stopping chemotherapy in those 117 cases included treatment completion (67%), toxicity (12%), disease progression (8%), or death (3%). In only 4% of cases was chemotherapy discontinued due to patient refusal, and in 3% of cases a patient was lost to follow up. Conclusions. In this largely rural population, only a small proportion of cases stopped adjuvant chemotherapy early due to patient-attributable factors; most treatment termination was due to clinical indications. Review of practice patterns using only administrative data may not reveal the actual reasons for treatment discontinuation. Further study of underlying factors of early termination is needed to design appropriate interventions to promote completion of prescribed therapy.

No significant financial relationships to disclose.
The utilization of new oncology drugs: A global perspective
Authors: Jönsson B. , Lichtenberg F. , Lundkvist J. , Svedman C. , Wilking N.
Published: March 2020

6612

Background: A number of new innovative cancer drugs have recently been approved or are in the process of being approved. We have analysed the access and uptake of 65 oncology drugs in 25 countries (19 European countries, Australia, Canada, Japan, New Zealand, South Africa and the USA) over a 10 year period based on sales data provided by IMS Health. Methods: We calculated an index of number of patients treated based on sales per inhabitant or per person who died from a specific cancer type. The age composition (vintage) of the drug arsenal used was calculated based on sales for cancer drugs introduced before 1995; between 1995–1999, 2000–2002 and after 2002 respectively. The vintage of the drug arsenal used was also analysed in relation to different economic and health care system characteristics. We performed three types of analysis of the effect of cancer drug vintage on cancer survival and mortality using difference-in-difference research designs. Results: Different patterns of uptake were seen in the countries studied, both with respect to speed of uptake and level of use. Fast uptake of most new drugs was seen in Austria, France, Switzerland, Spain and the USA, and slow uptake as well as low usage was seen in Poland, Hungary, New Zealand, South Africa and the UK. For some of the most recently approved drugs the variation in uptake is especially marked. The vintage of the cancer drug “arsenal” used also differs significantly between countries. Nearly half (44%) of the observed improvement in the two-year cancer survival rate between 1992 and 2000 at 50 USA cancer centres could be attributed to the use of newer cancer drugs. Around one sixth (14% − 19%) of the inter-country differences in 5-year cancer survival rates across 5 major European countries is due to differences in the uptake of newer drugs (post-1985) in each country. Nearly one third (30%) of the decline in cancer mortality rates seen during the period 1995 –2003, could be accounted for by the use of newer drugs. The observed decrease in mortality of 16% would have been only 11% if newer drugs had not been used. Conclusions: Patient access to innovative cancer drugs varies significantly between countries affecting mortality rates, and further research is needed into the determinants and consequences of these variations.

No significant financial relationships to disclose.
Removing barriers to clinical research in community hospitals—The Fox Chase Cancer Center Partners experience
Authors: O'Grady M. A. , Cohen S. J. , Keeley P. A. , Sein E. , Miller B. J. , Engstrom P. F.
Published: March 2020

6614

Background: Although the majority of cancer patients are treated in community hospitals, resources to support community clinical trials are often limited. The Fox Chase Cancer Center Partners (FCCCP) initiative is a large academic and community based oncology program in the Delaware Valley. We hypothesized that a detailed clinical research assessment within the 18 main community cancer research programs of the FCCCP would result in improved clinical trial accrual. Methods: The FCCCP clinical team completed research assessments at 10 affiliated community hospitals during 2004–2006 to evaluate active trials, research nurses and data managers, and research barriers. Institutions were benchmarked for staffing, processes, outreach, and quality improvement. Results were presented to administration at each hospital and impact on research accrual recorded. Results: In 2004, 371 patients were treated on clinical trials at 18 FCCCP community research programs. The median number of data managers, research nurses, and open protocols per site was 0.7, 1.6 and 48 respectively. The most common perceived barriers to accrual by investigators and research staff were regulatory burden, time, and awareness. Recommendations included: improved tumor registry identification of clinical trial candidates, increased staffing, improved web-based outreach, and targeted research affiliations. With regulatory burden a significant research barrier, the following IRB streamlining processes were recommended: NCI Central IRB, for-profit IRBs, IRB reciprocity, and centralized health system IRBs. With implementation of recommendations, 10/18 IRBs have transferred to the NCI-Central IRB for phase III cooperative group studies. The median number of data managers and research nurses per site increased to 1.25 and 1.7 respectively. Although the median number of open trials per site remained at 48, accruals to clinical trials increased to 805, representing a 116% increase. Conclusions: Research assessments are feasible in a large academic-community hospital partnership program and result in best practice recommendations with increased clinical trial accrual. Larger scale implementation of research infrastructure in community oncology programs is warranted.

No significant financial relationships to disclose.
Assessment of medication safety in the outpatient setting
Authors: Hoverman J. R. , Shuey K. M. , Richardson D. , Hansen K. , Dugger P. C.
Published: March 2020

6631

Background: US Oncology provides the pharmacy and drug infusion support for over 700 medical oncologists and hematologists. As such medication safety is a principle concern for the delivery of quality care. As described earlier, a survey of affiliated practices indicated three areas of concern: 1) no uniform reporting mechanism, 2) no standard double check mechanism, and 3) variable inclusion of medication safety procedures and reporting into practice operations. This report describes the first three years experience and proposals for continuing improvement. Methods: An online reporting tool was made available to all practices. 337 practice sites and 35 practice groups were monitored. The first hour of chemotherapy (1HC) was used as the denominator for all occurrence calculations. All reporting was voluntary. Occurrences were rated as to severity, from 1 (error detected before any steps towards completion) to 7 (error resulting in death of the patient). The occurrences were categorized according to process, either in prescribing, calculation of doses, lab or allergy issues, or matching the mixed dose to the order or in administering a mixed dose. In each circumstance a near miss or failure to double check was determined. The total experience for the network was determined for 2004 and 2005 with projected data for 2006. Results: The 1HC numbers used as denominators are: 2004–534,542: 2005–534,606: 2006 –542,000. Occurrences with error rates were: 2004 –1,723 (0.32%), 2005 –2,467 (0.46%), 2006 –2,653 (0.49%). The percent practices participating were 70%, 83% and 75% for 2004, 2005 and 2006 respectively. When considering only reporting practices the occurrence rates were: 2004 –0.45%, 2005–0.55%, 2006–0.65%. The percent occurrences with temporary or permanent harm to the patient dropped from 19% in 2004 to 16% in 2006. A failure to double check was a contributing factor in 57% in 2004, 42% in 2006. Conclusions: An anonymous reporting mechanism resulted in an increase in occurrence reporting. An education program led to fewer failures to double check and a decrease in events causing harm to patients. Next steps include enhanced feedback to practices and the use of an EHR to improve processes. The malpractice environment in some areas inhibits reporting.

No significant financial relationships to disclose.
Financial conflicts of interest amongst abstracts, speakers, and planning committee members at the American Society of Clinical Oncology Annual Meeting
Authors: Johnston K. L. , Go R. S.
Published: March 2020

6635

Background: Financial conflicts of interest (COI) in medical research are an issue under scrutiny due to a potential risk for biased information. The objective of this study was to survey the extent of self-reported financial relationships with industry amongst abstracts, speakers, and planning committee members at the American Society of Clinical Oncology (ASCO) Annual Meeting. Methods: We used the 2005 and 2006 ASCO meeting program books to tally the total number of abstracts (all types), speakers for education (faculty) and abstract sessions (discussant), as well as planning committee (education and scientific) members (data available only for 2006). The number and nature of financial disclosures were noted. COI categories include: employment, consultant role, stock ownership, honoraria, research funding, expert testimony, or other remuneration. Results are presented as an average over 2 years whenever appropriate. Results: There were approximately 4,396 abstracts presented, 678 speakers, and 301 planners each year. COI were reported in 27%, 46.8%, and 67.4% amongst abstracts presented, speakers, and planners, respectively. Within reported COI, the most common were consultant or advisory role (24.6%), honoraria (21.7%), research funding (21.7%), employment (15.2%), and stock ownership (12.6%). Amongst abstracts with COI, 27.4%, 27.1%, and 45.5% reported 1, 2, or ≥ 3 COI, respectively. Amongst speakers and planners with COI, 35.9%, 38.1%, and 26% reported 1, 2, or ≥ 3 COI, respectively. Notably, COI disclosure was not provided by 14.8% of the speakers on time for the program book publication. Conclusions: Financial COI are prevalent amongst presentations and more so amongst speakers and planners at the ASCO annual meeting. A large proportion of speakers failed to provide disclosure on time. The overwhelming majority of the disclosures were COI other than research funding. While the actual impact of COI on the clinical and research practices of oncologists and researchers cannot be determined from our study, the potential for such influence is significant.

No significant financial relationships to disclose.