bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of factors associated with recruitment in hematological clinical trials: A retrospective study
Authors: Amireault C. , Camden S. , Poulin J. , Lemieux J.
Published: August 2020

6567

Background: Recruitment of patients in cancer clinical trials has been reported to be between 3%–5%. Very few data come from Canada. Methods: The objective was to measure the recruitment and its associated characteristics in hematology clinical trials for malignant diseases. This was a retrospective cohort study using charts review in a tertiary hematology centre in Québec City, Canada. Clinical trials opened between 2002 and 2008 were selected. For each protocol, main criteria were used to define the population under study (e.g., stage IV Hodgkin lymphomas first-line). If the patient filled the main criteria, all eligibility criteria (inclusion and exclusion criteria) of the protocol were assessed. Results: Among all charts reviewed, 697 patients were identified in 17 protocols. However, as a patient could be assessed for more than one protocol if applicable, this population reached 1,394 observations. The study population filling the main criteria of a protocol included 195 observations in 17 protocols (186 different patients). Only 9.7% (8.2–11.4) filled all the eligibility criteria and 3.3% (2.5–4.4) were recruited among all charts reviewed (1394 observations). However, theses rates reached 68.2 % (61.2–75.1) and 23.1 % (17.9–29.8), respectively, among patients meeting the main criteria of a protocol (195 observations). Recruitment in the population who filled all eligibility criteria (inclusion and exclusion criteria) was 33.8% (26.7–42.5). Patient's sex, age, comorbidities, doctor's sex, doctor's age and protocol characteristics were not associated with recruitment in the population filling the main criteria, but having a note in the chart about the protocol appears to be associated with higher recruitment (p < 0.0001). The most common reasons for not being recruited were as follow (could have more than one reason): 40.7% not fulfilling all eligibility criteria, 31.3% protocol not being proposed and 22.7% patients’ refusal. Patients reasons for refusals were (could have more than one reason): 50% unknown, 26.5% fear of side effects, 20.6% too many visits, 14.7 % already enough anxious about disease, other. Conclusions: The largest barriers about recruitment were protocol ineligibility and protocol not being proposed by the medical team.

No significant financial relationships to disclose.
Disparities in colorectal cancer (CRC) screening in an underserved population
Authors: Lin A. Y. , Kouzminova N. , Lu T.
Published: August 2020

6569

Background: CRC is a common, potentially lethal, yet preventable disease. Screening tests for CRC are known to reduce the rate of death by detecting early cancer. To evaluate factors associated with the practice and impact of CRC screening, we reviewed a decade of CRC patients treated at an inner-city hospital. Methods: Under an IRB-approved protocol, data, including demographics, stage at diagnosis, utilization of screening tests, and insurance status, were obtained from CRC patients, at age 50 or above at diagnosis, treated between 1994 and 2004 at Santa Clara Valley Medical Center, a public hospital in the Silicon Valley. Chi-square test and multivariate regression analysis were used to evaluate factors associated with screening and its outcome. Results: We identified 331 cases of CRC patients who met the study criteria, with 50.5% (167) male and 49.5% (164) female patients. By ethnicity 36.6% (121) of the patients were Asian, 3.6% (12) Black, 22.8% (72) Hispanic, 37.8% (125) white, and 0.3% (1) other ethnicity. Only 5.7% (19) of the patients had been diagnosed by a screening colonoscopy, and 5.4% (18) of the patients had screening fecal occult blood test (FOBT). As a result, 9.4% (31) patients were diagnosed after either a positive colonoscopy or FOBT. Their stage distribution is presented in the table below. There was no association between the screening practice and gender, age, race or insurance status in this cohort. CRC diagnosed by screening test was significantly associated with survival benefit (p<0.01). Multivariate regression analysis revealed that survival was significantly associated with stage (p<0.05) and Hispanic race (p<0.01); but not screening test or insurance status. Conclusions: In this underserved population, even with a low rate of screening tests, screening for CRC is associated with earlier stage of CRC presentation which has been linked with survival benefit. Further studies are needed to identify barriers to CRC screening in this inner-city population.

[Table: see text]

No significant financial relationships to disclose.
Cost-effectiveness of targeting chemotherapy with the 70-gene prognostic signature in early-stage breast cancer (ESBC) patients
Authors: Tong K. B. , Chen E. , Brink G. , Bender R. , de Snoo F. , Malin J.
Published: August 2020

6570

Background: The 70-gene microarray test (MammaPrint) has been shown to provide additional prognostic information to clinicopathologic risk assessment for women ESBC; however, the cost-effectiveness of this strategy is not well understood. Methods: The objective of this analysis was to estimate the incremental benefits, costs, and cost-effectiveness of the treatments guided by the 70-gene signature versus Adjuvant! Software (AS) to decide on the use of adjuvant chemotherapy for women ≤61 years with lymph node negative, HER-2 negative ESBC with estrogen receptor (ER) positive or negative disease. A Markov model with a lifetime horizon and three health states (alive without recurrence, death from cancer and death from other causes) was constructed using TreeAge Pro software. Risk classification and patient outcomes data were based on a multi-center 70-gene signature validation study. Efficacy of chemotherapy derived from published meta-analysis of clinical trials. Costs and health utilities were obtained from the literature. Costs and benefits were discounted 3%/year. Results: Compared to AS, the 70-gene signature strategy resulted in 35% of patients being reassigned to a different risk classification and avoided chemotherapy in 9% of patients. In the base case, the 70-gene signature strategy was cost neutral (lifetime costs per patient: $178,811 versus $178,893 for the 70-gene signature and AS strategy). Moreover the 70-gene signature strategy was associated with an increase of 0.13 life years (LYs) and 0.16 quality adjusted life years (QALYs). The model results were sensitive to the cost of 70-gene signature test, cost of adjuvant chemotherapy, and relative risk reduction associated with chemotherapy; however, the 70-gene strategy remained cost-effective across a wide range of assumptions. Conclusions: In this analysis, the 70-gene signature was associated with a reduction in chemotherapy use and an increase in life expectancy. The 70-gene signature appears to be a cost-effective strategy for obtaining additional information to guide the decision to use adjuvant chemotherapy in patients with lymph node negative ESBC.

[Table: see text]
Admissions for chemotherapy-related serious adverse effects (CR-SAEs) and rates of mortality among community cancer center patients
Authors: Rao S. R. , Hassett M. , Schwartz J. H. , Maloney B. , Jacobson J. O.
Published: August 2020

6571

Background: Data regarding CR-SAE's come predominantly from clinical trials; little is known about the experiences of cancer patients treated in community settings. Our goals were to describe admissions for CR-SAE's among cancer patients treated in a community setting and to identify rates and predictors of mortality for admitted patients. Methods: We conducted a prospective cohort study of adult cancer patients (excluding acute leukemia and stem cell transplant patients) admitted to a community hospital January 2003-December 2006. A multidisciplinary panel of cancer providers determined which admissions were chemotherapy-related. We identified the type of SAE, outcome of each admission, time form chemotherapy to admission and from admission to discharge/death, and the disease and treatment characteristics of each patient. Statistical analyses included Chi-square, ANOVA, and logistic regression. Results: 227 patients experienced 258 admissions for CR-SAE's (55.5% female; median age 68, range 17–89). The most common cancers were colorectal (18.5%), lung (18.1%), lymphoma (16.3%), and breast (13.7%). Most chemotherapy was palliative (53.5%). SAE's were categorized as gastrointestinal (46.1%), infectious (31.4%), hematologic (9.3%), cardiac (8.1%), and other (5.0%). Approximately 7.4% of admissions led to fatalities, with a median of 9 days (range 1–35) from admission to death. Fatalities were more frequent among patients receiving palliative versus adjuvant/curative chemo (10.1% vs. 4.2%; p = 0.07) and among patients experiencing infectious vs. other SAE's (13.6% vs. 0–9.5%; p = 0.07). On multivariable analysis, palliative therapy was a borderline-significant predictor of mortality (OR 2.8; 95% CI 0.9–8.4; p = 0.07). The average time from chemotherapy to admission was shorter for fatal vs. non-fatal admissions (3.6 vs. 7.7 days; p<.01). Conclusions: Fatalities during admissions for CR-SAE's in a community cancer center are relatively uncommon and are not associated with age or type of SAE/cancer. Further investigation regarding predictors of mortality following palliative chemo may be warranted. Chemotherapy-related mortality in the palliative care setting may be a valid quality indicator.

[Table: see text]
Health care disparity: An analysis of breast, colon, and lung cancer
Authors: Dubey S. , Griffin A. , Hwang J.
Published: August 2020

6579

Background: Lung cancer patients are associated with feeling of guilt about their disease (Schmidt ASCO 2006) and less likely to be referred to specialists (Wassenaar ASCO 2006). They are also commonly affected by smoking related comorbidities. A study was undertaken to evaluate whether treatment differences between lung and other cancers exist. Methods: Public access data for the year 2005 from the National Cancer Data Base (NCDB) was analyzed. Treatment data were categorized by institution (teaching/research [TR] versus community cancer center [CC]) and tumor type (non-small cell lung cancer-NSCLC, breast, colon cancer). Descriptive analysis was performed with student T tests for proportions. Results: The analysis included 18,960 NSCLC patients from a CC and 33,924 from a TR. More patients at TR than CC had surgery: Stage I 65% vs 52% (p < 0.001), Stage II 35% vs 22% (p < 0.001), respectively. The frequency of chemoradiation for stage I and II was higher in CC than TR: stage I 6% vs 3% (p = 0.10), stage II 19% vs 9% (p = 0.004). The frequency of no first course treatment at initial presentation at CC and TR were the following: stage I 15% vs 6%, stage II 18% vs 8%, stage III 21% vs 19%, stage IV 30% vs 24%. For breast and colon cancer, no major differences in no first course treatments were seen between TR and CC in a stage based analysis. More patients with NSCLC (21.2%) did not receive first course treatment in comparison to breast (3.4%, p < 0.001) or colon cancer (7.8%, p < 0.001). These differences were maintained in stage based analysis of the three tumor types. Conclusions: NSCLC patients are at higher risk of not receiving treatment as opposed to those with breast and colon cancer. While medical comorbidities in lung cancer patients may affect these treatment decisions, we noted a higher incidence of no first course treatment in CC than TR centers. For stage I and II, the frequency of no first course treatment in a CC was twice that of a TR. Such institution based differences were not noted in breast and colon cancer.

No significant financial relationships to disclose.
A willingness-to-pay study of vascular endothelial growth factor inhibitors among patients with advanced non-small cell lung cancer
Authors: Goldberg R. J. , Jang R. W. , Leighl N. B.
Published: August 2020

6581

Background: Bevacizumab, a recombinant antibody which neutralizes vascular endothelial growth factor (VEGF), has been approved for the treatment of advanced non-small cell lung cancer (NSCLC). Costs of novel anticancer medications such as bevacizumab can be prohibitive for many lung cancer patients. This study sought to determine patients’ willingness-to pay (WTP) for bevacizumab and identify Canadian patient attitudes towards unfunded chemotherapeutic drugs. Methods: Participants attending outpatient lung cancer clinics at a major Canadian cancer center were given information pertaining to the risks and benefits of treatment with bevacizumab and were then asked about their WTP for this agent. Demographic and socioeconomic data were collected. A semi-structured interview was utilized to define the factors that limit patient access to unfunded chemotherapeutic agents. Results: 35 advanced NSCLC patients with a median age of 64.5 years and a median income of $40,000-$60,000 CAD consented to participate. Overall, participants were willing to pay a median of $75 CAD ($19-$250 CAD) per month for VEGF inhibitors, much less than the market cost of $8,000 CAD per month. 25 of 35 (71.4%) participants felt that the government should cover 100% of the drug cost, while 0%, 2.9%, 5.7%, and 20% of participants felt that the government should cover 0%, 25%, 50%, and 75% of the cost, respectively. Qualitative themes that arose included: (1) financial barriers are the primary obstacle in gaining access; (2) patients understand that the government cannot fund all novel cancer therapies; (3) patients are not willing to take loans or seek treatment outside of Canada without the prospect of cure; and (4) patients believe their oncologist will discuss all potential therapies, irrespective of access issues. Conclusions: Novel chemotherapeutic agents are unaffordable for the majority of NSCLC patients. Most patients would like the government to cover the cost of treatment, but many agree that the modest benefits of novel therapies may not always justify the large associated cost for government and publicly funded healthcare systems.

[Table: see text]
Cost-effectiveness of a health care provider-directed intervention to promote colorectal cancer screening
Authors: Shankaran V. , Luu T. H. , Nonzee N. , McKoy J. M. , Zivin J. G. , Ashford A. R. , Lantigua R. , Frucht H. , Scoppettone M. , Bennett C. L. , Gorin S. S.
Published: August 2020

6583

Background: Colorectal cancer (CRC) screening remains underutilized. Prior studies reported the cost-effectiveness of interventions to improve CRC screening, but none have been replicated in the setting of small medical practices. We recently conducted a randomized trial of an academic detailing strategy within 264 small physician offices in New York City. The objective of this analysis is to assess the cost-effectiveness of this intervention. Methods: 264 physician offices were randomized to usual care or to a series of ‘academic detailing’ visits from health educators trained in evidence-based CRC screening guidelines. CRC screening rates were measured at baseline and 12 months. Intervention-related costs were categorized as fixed or intervention delivery costs. The incremental cost effectiveness ratio (ICER) was expressed as cost per percentage point increase in CRC screening. Each practice contained an average of 4 physicians. Sensitivity analyses were estimated by varying the number of physicians per practice and accordingly, intervention delivery costs. Results: Academic detailing resulted in a 7% increase in CRC screening with colonoscopy. The cost of the intervention was $147,865. The ICER was $21,124 per percentage point increase in CRC screening. Sensitivity analyses that varied the intervention delivery costs by the average medical practice size were associated with ICERs ranging from $13,361 (8 physicians/office) to $36,109 (2 physicians/office) per percentage point increase in CRC screening rates. Conclusions: A multi-component academic detailing intervention conducted in small urban practices was clinically effective, but was not cost-effective when compared to other reported low-intensity patient-directed and infrastructural interventions ($131-$1,161 per percentage increase in CRC screening). (Table) While academic detailing may be more cost-effective in physician practices of larger size, new cost-effective approaches in small community practices are needed.

[Table: see text]

No significant financial relationships to disclose.
Review of postmarketing surveillance of molecular targeted anticancer agents in Japan
Authors: Miura Y. , Kami M. , Morita T. , Tsubokura M. , Takei N. , Murashige N. , Hori A. , Komatsu T.
Published: August 2020

6598

Background: Since the safety profile of molecular targeted anticancer agents is different from that of conventional anticancer agents, the safety information is limited. Although postmarketing surveillance (PMS) on safety is important, the appropriate methods of PMS have not been established. Methods: We investigated PMS methods, patients’ performance status (PS), and safety of the eight molecular targeted anticancer agents (imatinib, rituximab, trastuzumab, gefitinib, gemtuzumab ozogamicin [GO], bortezomib, bevacizumab, erlotinib) approved in Japan. We excluded sunitinib and sorafenib as the PMS of these agents were ongoing. Results: Besides PMS of gefitinib, seven PMS enrolled all the patients that received the study agents. The inclusive type of PMS was required at approval of the latest four agents, GO, bortezomib, bevacizumab, and erlotinib. The total number of enrolled patients was 8,776. Seven PMS of imatinib, rituximab, trastuzumab, GO, bortezomib, bevacizumab, and erlotinib enrolled 309, 2,575, 1,142, 316, 666, 2,698, and 1,070 patients, respectively. Data on the frequencies of patients with PS 3–4 were available in five of seven PMS, which were 7%, 7%, 20%, 3%, and 0.1% in PMS of rituximab, trastuzumab, GO, bortezomib, bevacizumab, respectively. Frequencies of severe adverse events were described in four of seven PMS, which were 3–6%, 0.3–4%, 0–45, and 0–2% in PMS of imatinib, rituximab, bortezomib, and bevacizumab, respectively. Interstitial lung disease related to Bevacizumab was unknown in premarketing studies and was observed in 0.4% in PMS. Drug related mortality rates were described in four of seven PMS, which were 1%, 8%, 3%, and 2% in PMS of rituximab, GO, bortezomib, and bevacizumab, respectively. Conclusions: Although PS varied among PMS of different molecular targeted anticancer agents, patients with poor PS were not included in most PMS. Disclosure of PMS results was insufficient. Further investigation on appropriate methods of PMS and its disclosure is warranted.

No significant financial relationships to disclose.
Clinical utility of routine proteinuria evaluation in the treatment decisions of patients receiving bevacizumab for metastatic solid tumors: A retrospective study
Authors: Yeh J. , Frieze D. , Martins R. , Carr L.
Published: August 2020

6599

Background: Bevacizumab is an anti-VEGF monoclonal antibody approved for use in metastatic breast, colorectal, and non-small cell lung cancer patients. In the pivotal Phase III clinical trials, Grade 3/4 proteinuria occurred in <5% of patients. The manufacturer recommends monitoring for the development of proteinuria but does not provide specific recommendations, except to discontinue treatment if the patient develops nephrotic syndrome. This retrospective analysis describes the incidence, severity, and cost of routine proteinuria monitoring in patients with metastatic solid tumors. Methods: A retrospective chart review was performed in our institution from June 1, 2005 to November 30, 2007. Patients treated with bevacizumab and seen in the breast, lung, and gastrointestinal cancer clinics were included. The primary endpoints are the incidence and severity of elevated proteinuria and the frequency of changes in bevacizumab due to elevated proteinuria. The secondary endpoints include analysis of the cost of routine proteinuria monitoring and to describe the correlation of proteinuria with bevacizumab-induced hypertension and other patient co-morbidities. Results: 243 patients were included in the analysis. Only 1.2% (3 of 243) of patients developed Grade 3/4 proteinuria. One of these patients had prior chronic renal insufficiency, while the other two patients had hepatitis and hepatocellular carcinoma. Seven patients developed Grade 3/4 bevacizumab-induced hypertension, however this did not correspond with the development of proteinuria. Over $130,000 was charged to patients for monitoring of proteinuria. Conclusions: These results demonstrate that clinically significant proteinuria is rare and routine proteinuria monitoring is associated with high cost.

[Table: see text]

No significant financial relationships to disclose.
Tumor registry versus physician medical record review: A head-to-head comparison of malignant pancreatic neuroendocrine tumor (mPNET) cases
Authors: Manasanch E. E. , McDade T. P. , Bodnari A. , McKinney J. , Sullivan M. E. , Whalen G. F. , Piperdi B. , Rosmarin A. G. , Tseng J. F.
Published: August 2020

6600

Background: Researchers have underutilized single-institution tumor registry (TR) data, instead using researcher medical record review and/or personal, departmental or institutional databases to identify patients with particular malignancies. However, TR data is becoming increasingly prominent on a national level through broader use of the National Cancer Database (NCDB). We selected mPNETs as example to compare the accuracy of TR identification of these tumors with physician medical record review (MD Review). Methods: For MD Review, the health information services department of a single academic medical center was queried for all patients with pancreatic ICD9 codes (157.0–157.9; 211.6–211.7) January 2000-August 2008. A single physician reviewer analyzed computerized and paper medical records and identified mPNET cases. For TR data, mPNET patients were identified using the TR database with assistance of TR staff by two separate strategies. From January 2000-December 2006, patients were identified by using diagnosis codes from manual review of admission, discharge, clinic and pathology reports. From January 2007-August 2008 the TR used an automated case finding program (CAL by C/NET, California, USA) that downloaded cases with terms and codes related to malignancy. All MD Review- and TR-identified mPNET cases were reviewed by a second investigator blinded to identification strategy to assure consistency of mPNET definitions. Results: Using MD Review, 1194 pts with pancreatic ICD9 codes were identified. After MD Review, 42 mPNET patients were identified and confirmed. In comparison, TR identified 17 patients, of whom 5 were not identified by MD Review. Of the 47 patients identified by either strategy, TR identified 17/47 (32.6%) patients, whereas MD Review identified 42/47 (89.4%). TR identification rate in time periods 1 and 2 were 30% and 40%, respectively. Conclusions: Analysis of an academic tumor registry demonstrates that a substantial proportion of mPNET cases are missed when compared to ICD-9 identification and physician medical record review. Since MD review is imperfect, the TR may be even less effective at identifying PNETs than our data suggest. This may be applicable to other tumor registries and TR-based national studies.

No significant financial relationships to disclose.
Analysis of the rate of non-target disease progression in patients with stable or responding target disease by the Response Evaluation Criteria in Solid Tumors (RECIST)
Authors: Borradaile K. , Ford R.
Published: August 2020

6603

Background: RECIST suggests progression of non-target disease is rare in patients with stable or responding target disease. We reviewed outcomes by RECIST to determine the rate of non-target (NT) progressive disease (PD). Methods: Outcomes of RECIST-based blinded independent central review (BICR) of 962 breast and colon cancer patients were used to identify 514 patients that had a progression event in order to determine the incidence of NT-PD. The radiographs of the 55 patients that had NT-PD were further reviewed by the authors (KB, RF) to confirm the NT-PD was “unequivocal.” To be considered unequivocal, there had to be a definite, substantial increase in the size of one or more metastatic NT lesions that was clearly not related to differences in imaging technique. To confirm the subjective nature of the “unequivocal progression,” the lesion(s) upon which PD was assessed was measured and a 20% increase in the lesion(s) since nadir was required. Results: Of the patients with PD, 11% (55/514) progressed only on worsening of NT disease. In 82% (45/55) of cases where the NT-PD was unequivocal, either the target disease was increasing but had not met the quantitative requirement for progression or the increase in NT disease would have resulted in target progression had the NT site(s) of disease been included with the baseline target lesions. Of the remaining 18% (10/55) where the two criteria described above did not apply, and an additional evaluation was performed, the next evaluation confirmed PD. Conclusions: Progression on the basis of NT disease can be reliably assessed if the target disease has started to increase from the nadir or if the increase in NT disease is significant enough to have resulted in target disease progression if classified as such. If one of the above criteria is not met, it is recommended that treatment continue until progression can be confirmed at the next evaluation.

No significant financial relationships to disclose.
Association of adolescent and young adult cancer treatment trial activity with a national mortality reduction benefit in the United States
Authors: Bleyer A. , Friedman S. , Finnegan S. , Montello M. , Budd T. , Anderson B. , Trimble E. L.
Published: August 2020

6605

Background: Adolescent and young adult (AYA) cancer patients in the U.S. have had less mortality and survival improvement than have children or older adults with cancer. Because <3% of 20–35 year-olds are entered onto national cancer treatment trials (NCTT), in contrast to ∼50% of children, initiatives were undertaken during the past 6 years to increase NCTT AYA participation. Methods: NCTT accrual data were obtained from the Cancer Treatment Evaluation Program, NCI. Survival, mortality, and incidence data were obtained from the NCI Surveillance, Epidemiology, and End Results (SEER) program. Results: In comparison of 2002–2006 with 1996–2001, the average annual NCCT accruals of patients 15–39 years of age increased from 1,032 to 1,792, the estimated proportion of patients in this age group on NCTT increased from an average of 4.2% to 6.5%, and the proportion of all NCCT accruals (of all ages) that were in the 15–39 year age group increased from an average of 5.2% to 8.2%. Of the 11 national NCTT groups, the pediatric group (Children's Oncology Group [COG]) had the largest AYA accrual number and increase, enrolling more than twice the number of 15–39 year-olds than any other cooperative group and 1/3 of all of them. Among 15–29 year-olds nearly all of the increased accrual occurred in patients with leukemia or lymphoma, in whom the ratio of the national death rate to SEER incidence fell below the projected linear regression for this ratio in each year during 2002–2005. Conclusions: In the U.S., COG is now contributing more AYA patients to NCTT than any adult cooperative group, suggesting that the adult-treating groups and cancer centers have increased capability to increase AYA accrual and should complement the pediatric effort. That the disease group that accounted for nearly all of the increase also had a concomitant reduction in deaths relative to incidence may be cause and effect. These favorable trends should encourage implementation of the clinical trial recommendations of the NCI Program Review Group in AYA Oncology ( http://planning.cancer.gov/disease/AYAO_PRG_Report_2006_FINAL.pdf ) that are being implemented in part by the LIVESTRONG Young Adult Alliance (Closing the Gap: A Strategic Plan).

[Table: see text]
Locally advanced prostate cancer: A population-based study of treatment patterns and predictors
Authors: Lowrance W. , Eastham J. , Jacks L. , Yee D. , Scardino P. , Elkin E.
Published: August 2020

6606

Background: Treatment of locally advanced prostate cancer (LA PCa) is controversial, but recent trial results demonstrate superior outcomes for combination therapy compared to monotherapy. We aimed to identify treatment patterns, predictors, and trends in a population-based cohort of men with LA PCa. Methods: From Surveillance, Epidemiology and End Results (SEER) cancer registry records linked with Medicare claims, we identified men age 65 and older diagnosed with clinical stage T3 and T4 nonmetastatic PCa from1995 through 2002. Using Medicare claims, we classified treatments (radical prostatectomy (RP), radiation therapy (RT), or androgen deprivation (AD)) received within 6 and 24 months of PCa diagnosis. We assessed trends over time and used multivariable logistic regression to assess sociodemographic and clinical predictors of treatment. Results: The Table shows the distribution of treatments given within 6 months following diagnosis among 3,412 men with LA PCa. Approximately one third of patients were treated with a combination of RT and AD (31%), 46% received monotherapy, and 17% received no active treatment. Between 1995 and 2002, the most notable change was an increase in use of the combination of RT and AD as primary therapy. The percent of patients who received RT and AD rose from 16% in 1995 to 39% in 2002. Significant predictors of receiving combination therapy over the study period were age, race, urban residence, marital status, clinical stage, year of diagnosis, and Charlson comorbidity score. All results were similar when we examined treatments received within 24 months of diagnosis. Conclusions: Patterns of treatment for locally advanced prostate cancer shifted during the study period, with the combination of RT and AD becoming the most common treatment modality. This movement toward combination therapy for LA PCA is encouraging, given recent evidence of the superiority of such therapy in these patients. Future efforts should focus on further increasing the use of multimodality therapy in LA PCa.

[Table: see text]

No significant financial relationships to disclose.
Does quality of treatment-related harms reporting affect conclusions about superiority of treatment?
Authors: Mhaskar R. S. , Kumar A. , Soares H. , Schell M. , Djulbegovic B.
Published: August 2020

6607

Background: It is often not known if harms were considered in the overall benefit-risk evaluation in deciding about the superiority of treatments. Here we present a study examining the relationship between researchers’ conclusions about the superiority of treatment with quality of treatment-related harms reporting. Methods: We reviewed all consecutive phase III randomized clinical trials (RCTs) conducted by Southwest Oncology Group from 1960 to 2003 (117 RCTs involving 139 comparisons enrolling 58,908 patients). We extracted data on primary outcomes [overall survival (OS), event free survival (EFS)], and treatment-related mortality (TRM). We classified the quality of reporting as good, intermediate or poor. Association of superiority of treatment and harms reporting was evaluated using chi-square test and meta-analytic techniques. Results: 76% of studies (106/139) reported TRM. Of these, the quality of reporting of harms was considered as “good” in 36% (38/106) of studies, “intermediate” in 55% (58/106), and “poor” in 9% (10/106). Investigators judged experimental treatments to be superior in 34% of trials (48/139) while standard treatment was superior in 66% (91/139). TRM data was reported in 75% (36/48) of results favoring experimental treatments and 78% (70/91) of results favoring standard treatments. There was no association between superiority of a treatment and TRM reporting (p = 0.80) or quality of harms reporting (p = 0.83). The pooled hazard ratio (HR) for OS in RCTs reporting TRM was 0.94 (95% CI: 0.90, 0.99) and for RCTs not reporting TRM was 0.99 (95% CI: 0.89, 1.09) (test of heterogeneity p = 0.06). The pooled HR for EFS among RCTs reporting TRM was 0.88 (95% CI: 0.83, 0.94) and for RCTs not reporting TRM it was 1.01 (95% CI: 0.79, 1.29) (test of heterogeneity p = 0.07). Additionally, the pooled HR for OS and EFS did not show any bias in reporting of harms according to harms reporting quality. Conclusions: Investigators’ conclusion regarding the superiority of experimental or standard treatment does not appear to be associated with outcome reporting bias for harms. Investigators judge both harms and benefits when they draw conclusions about treatment superiority.

No significant financial relationships to disclose.
Presentation of breast cancer in young women
Authors: Ruddy K. J. , Gelber S. , Tamimi R. , Schapira L. , Come S. , Kereakoglow S. , Lin N. U. , Winer E. P. , Partridge A. H.
Published: August 2020

6608

Background: Current guidelines for early detection of breast cancer do not adequately address diagnosis in young women. Furthermore, a lower suspicion for malignancy in this population may cause diagnostic delays. It is unknown how much the lack of routine screening and potential diagnostic delays contribute to the poorer outcomes of younger women. Methods: We surveyed women age <40 with recently diagnosed breast cancer in a prospective multicenter cohort study started in late 2006. We evaluated initial sign/symptom of cancer, time to first seeking medical attention, time from seeking medical attention to diagnosis, and patient factors associated with delays of >30 days in either timeframe. Chi square and Fisher's Exact tests were used to compare those with and without delays. Results: The first 222 women enrolled in the cohort are included in this analysis. Median age at diagnosis was 36 years (range 17–40). 79% of women initially identified their cancers through breast self exam. Only 6% were initially identified by clinical breast exam, 14% by breast imaging, 1% by systemic symptoms. While the median time between initial sign and seeking medical attention was 10 days (range 0–3,600), 54 women had >30 days between initial sign and medical attention (median 102, range 44–3,600). Similarly, median time from seeking medical attention to diagnosis was 21 days (range 0–2,970), yet 59 women had >30 days from attention to diagnosis (median 70, range 33–2,970). Preliminary comparison of women with and without delays did not reveal significant differences in age, race, education, marital status, or gravidity. Analyses will be updated and psychosocial factors, tumor subtype, and stage at diagnosis will be evaluated. Conclusions: In this large modern cohort of young women with breast cancer, nearly 80% presented with a self-detected breast abnormality, and most were diagnosed soon after they developed a sign/symptom. However, nearly 25% delayed seeking medical attention and 25% experienced a delay in diagnosis after seeking medical attention. Further research is warranted to compare delays between younger and older women, to evaluate delays in more diverse populations, to explore predictors of delays, and to assess for prognostic implications of delays in order to improve outcomes in young women.

No significant financial relationships to disclose.
Effect of social or health insurance status on outcome of patients with early breast cancer
Authors: Jueckstock J. K. , Scholz C. , Brandelik A. , Rack B. K. , Sommer H. L. , Janni W. J. , Friese K.
Published: August 2020

6609

Background: Recent studies in the US showed a relationship between state of social or health insurance of cancer patients and their overall survival (OAS). ([1] Banerjee M et al, Cancer. 2007;110:2169–2177. [2] Griggs JJ et al, J Clin Oncol. 2007;25:2522–2527. [3] Brookfield KF et al, Cancer. 2008.) In Germany 91% of all women have a compulsory health insurance whereas 9% have private health coverage. There are no pts without health insurance in Germany. Methods: In a retrospective analysis of 1846 German early breast cancer pts correlation between state of social and health insurance and OAS was investigated. 59.6% of the pts had a social insurance whereas 40.4% had none. 69.1% of the pts carried compulsory health insurance while 30.9% had private coverage. Among the pts with compulsory health insurance 56.6% had had a professional education and 41.5% were working whereas among the pts with private coverage 66.2% were professionally experienced and 43.9% were working. Age, tumor size, lymph node metastases, and tumor grading were well balanced between the two groups. 25.4% of all pts had undergone mastectomy and 72.6% had had a breast conserving therapy. In 2.0% of the pts no breast surgery was performed. 33.6% of all pts received adjuvant chemotherapy while endocrine therapy or radiotherapy was administered to 40.1% and 61.1% respectively. Results: OAS as expected was strongly correlated to established prognostic factors like age, tumor size, lymph node status, and grading (p < 0.001 respectively). However, OAS of the pts did not correlate to either social (p = 0.110) or health (p = 0.659) insurance state. Neither mattered the professional education of the pts concerning OAS (p = 0.217). Conclusions: Unlike the American results there was no correlation seen between state of social or health insurance for German early breast cancer pts. Thus, although pts with private coverage are supposed to receive more intensive medical care outcome for these pts concerning OAS does not exceed that of pts with compulsory insurance.

No significant financial relationships to disclose.
Cost-effectiveness analysis of a randomized study with stereotactic radiosurgery (SRS) alone versus SRS plus whole brain radiation therapy (WBRT) for patients with brain metastasis
Authors: Lal L. S. , Chang E. L. , Franzini L. , Arbuckle R. B. , Miller L. , Reasonda L. G. , Feng C. , Swint J. M.
Published: August 2020

6624

Background: This paper illustrates the incremental cost-effectiveness ratio (ICER) and cost-utility comparison of SRS alone versus SRS plus WBRT for brain metastasis. Methods: A decision analysis model, including subsequent treatment for recurrences, was developed and populated with data from patients randomized to either SRS alone (SA) versus SRS plus WBRT (SW), using costs from the healthcare institution perspective and outcomes based on actual life years saved (LYS) and quality-adjusted-life-years (QALYs). Utilities were captured through a time-trade -off methodology, utilizing three time horizons: 10 years, 5 years, and 1 year. Tornado diagrams and one-way sensitivity analyses were conducted to determine robustness of the model. Results: Fifty-eight patients were included in the final analysis, with 31 patients in the SA arm and 27 patients in the SW arm. The average cost of the SA arm is $119,000 versus $74,000 for the SW arm. The average effectiveness for the SA arm was 1.64 LYS versus 0.60 LYS for the SW arm. The ICER for total costs per LYS and QALYs were: $43,986 per LYS; $42,136 per QALY (10year); $43, 719 per QALY (5year); $44,686 (1year) for the SA arm. The surgical cost per LYS was $7,131 for the SA arm, and the radiation cost per LYS analysis was dominated. Tornado diagrams revealed that the following variables had the highest impact on the ICER: probability of being alive with SA in recursive partitioning analysis (RPA) class 2 and no recurrence; probability of no recurrence in RPA class 2 with SA; probability of being alive with SA in RPA class 2 and being treated for recurrence; probability of no recurrence in RPA class 1 with SA; and probability of being alive with no recurrence in RPA class 1 with SA. One-way sensitivity analysis exhibited a wide range variation for the first three of the above mentioned probabilities, with the final two having less variation. Conclusions: Compared to other interventions in the $50,000 to $100,000 per QALY cost-effectiveness range from an economic perspective, the application of SA, with subsequent surgical management of recurrences, is shown to be a reasonable treatment modality for brain metastasis.

No significant financial relationships to disclose.
Understanding among medical oncologists of the true monetary cost of therapy
Authors: Hoffman K. R.
Published: August 2020

6629

Background: While oncologists are educated to deal with the medical complexities of their treatment, a new side effect, that of financial toxicity, has arisen over the past several years. One of the major challenges in private practice is explaining the monetary cost of treatment to the patient. Methods: 50 medical oncologists agreed to take a survey judging their knowledge of the financial cost of the treatments used in patients with the five most common tumors treated in the office: breast cancer, non-small cell lung cancer, colorectal cancer, non-Hodgkin's lymphoma, and three other commonly treated cancers: chronic myelogenous leukemia, multiple myeloma and ovarian cancer. Treatment regimens in the adjuvant and first line metastatic setting were used. Physicians were asked to calculate the cost of treatments to the patient and not the acquisition price of drugs. They were asked to calculate the cost based a patient completing their adjuvant therapy or treatment in the first-line metastatic setting, which was defined by each practicioner. If desired, this included the use of maintenance therapy. A body surface area of 1.8 M2 for men and 1.6 M2 for women was used. Results: 39 medical oncologists completed the entire survey. Of these, 11 were in solo practicie. 27/39 were in practice over 15 years, while only 4 were in practice under 5 years. In almost all cases where intravenous or oral targeted therapies were used, the physicians under-estimated the actual cost of treatment to the patient by 25–40%. When ‘conventional‘ intravenous chemotherapy was used, they were either correct or over-estimated the cost of treatment by 25 to 33%, especially when generic substitution of trade name drugs were available. More importantly, the actual dollar difference was up to $50,000 when targeted therapies were in the treatment regimen but only around $5,000 when conventional treatments were considered. Nearly all the physicians were ‘within the ballpark‘ when dealing with the cost of oral medications. Conclusions: Medical oncologists have a poor understanding of the monetary costs of the newer treatments they are prescribing. More education is needed in the economics, including monetary cost-benefit analysis, of oncology practice so that we can better serve our patients and society.

No significant financial relationships to disclose.
A novel copay foundation assistance support program for patients receiving cancer therapy in cancer centers
Authors: Rajurkar S. P. , Presant C. , Bosserman L. , McNatt W.
Published: August 2020

6630

Background: With advent of newer CT (biotherapy, chemotherapy, and supportive care) treatment is becoming increasingly expensive for cancer pts. Pts enrolled with Medicare and commercial insurance plans often have large copay requirements with each treatment cycle. Often, these pts undergo significant financial hardship and some pts decline treatment. We have developed a novel support program to coordinate all copay assistance foundations (FDNs) in order to secure financial assistance to facilitate appropriate CT. Methods: In September, 2008 in our multi-site cancer center (11 oncologists, 6 CT sites), we developed a dedicated support program to coordinate pt applications to copay assistance FDNs including Healthwell, Cancer Care, Patient Access, Chronic Disease Fund, Beckstarnd Cancer, Lilly Cares, and Leukemia and Lymphoma Society. Pts requesting assistance with CT copay were enrolled in this program. A dedicated staff individual obtained information about diagnosis, insurance, income level, CT plan and associated co-pay requirements. Data was given to FDNs who determined the amount of monetary assistance. Responses of FNDs and administrative costs were analyzed. Results: Of 264 pts started initiating CT between September 2008 and December 2008, 25 (9.3%) requested assistance for either IV or PO treatments. The average interval between the submission of FDN application and date of determination of assistance was 10 days. Out of 83 applications (3.32 applications/pt), 50 (60%) were approved. Ultimately 22/25 pts received FDN support of $113,475. The most common reasons for denial were if the pt's income exceeded a certain level, exclusion of coverage of certain medications and the FDN being out of funds. The administrative costs associated with this program were $18,000/yr ($720/pt, or $217/application). Administrative costs were 1.64% of approved support. More difficulties were encountered with applications for oral CT than IV CT. Conclusions: Copay for CT drugs is a financial hardship for a significant number of pts. Coordinated resources must be provided and reimbursed to facilitate appropriate and sustainable cancer care. This program is a successful model for other centers.

No significant financial relationships to disclose.
Off-label chemotherapy use in a military treatment facility
Authors: Powers J. F. , Osswald M. B.
Published: August 2020

6631

Background: Off-label prescribing of chemotherapeutics is thought to be frequent but scant data exist to quantify its occurrence. The few studies evaluating off-label drug use in oncology show that the frequency ranges from 6.7% to 75%. This is the first known evaluation of oncology prescribing practices in a military treatment facility. Methods: After approval by the institutional review board, all outpatient chemotherapy orders from 2006 given in our clinic were reviewed. The date, drug name, dose, diagnosis, intention of therapy (curative, adjuvant, or palliative), and provider status (staff or fellow) were entered into an Excel spreadsheet. Package inserts for each drug were reviewed to determine if the medication was given on- or off-label. The dates of approval and label updates were further defined from FDA press releases. The percentage of courses and individual doses given off-label were calculated. Results: 186 patient charts were included in the analysis. Of 1,341 courses of chemotherapy, 50.48 % (n = 677) were given off-label. Of 3,299 doses of chemotherapy, 47.9% (1,581) were given off-label. Of the drugs prescribed, the most frequently dosed off-label were fluorouracil (n = 334), capecitabine (n = 229), traztuzumab (n = 123), leucovorin (n = 119), and carboplatin (n = 112). Of the 1,581 doses given off-label, 49% (n = 779) were given adjuvantly, 34% (n = 543) were given palliatively, and 16% (n = 259) were given curatively. Conclusions: Based on the current FDA labeling of chemotherapeutics, nearly half of the doses given in our outpatient clinic were off-label. However, the vast majority of our off-label use, such as adjuvant fluorouracil-based therapy, is considered standard of care and is supported by National Comprehensive Cancer Network practice guidelines and compendium listings. This retrospective analysis adds to the scant literature regarding off-label prescribing practices in oncology.

No significant financial relationships to disclose.